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Information on EC 3.4.21.53 - Endopeptidase La and Organism(s) Escherichia coli and UniProt Accession P0A9M0
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3.4.21.53 Endopeptidase LaSpecify your search results
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- 3.4.21.53
-
antiretroviral
- transcriptase
- cathepsins
- plasminogen
- coagulation
-
hiv-infected
- thrombin
- elastase
-
virological
- nucleoside
- neutrophil
- viruses
- endothelial
- pancreatic
- chymotrypsin
- lysosomal
- cd4
- collagen
- leukocyte
- plasmin
-
caspase
- calpains
- proteasome
- platelet
- metalloproteinase
-
amyloid
-
anticoagulant
- clot
- kallikreins
- amylase
- heparin
- fibrinogen
- upa
- venom
- urokinase
- fibrin
- sars-cov-2
-
mast
- covid-19
- coronavirus
-
zymography
-
thrombotic
- antithrombin
- papain
-
urokinase-type
- pai-1
-
fibrinolytic
-
granzyme
-
tissue-type
- tryptase
- medicine
- biotechnology
- agriculture
- diagnostics
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
protease, serine protease, clpxp, lon protease, lonp1, protease la, atp-dependent lon protease, protease lon, aaa+ protease, ms-lon, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP-dependent Lon proteinase
-
-
-
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ATP-dependent protease La
-
-
-
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ATP-dependent serine proteinase
-
-
-
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Escherichia coli proteinase La
-
-
-
-
Escherichia coli serine proteinase La
-
-
-
-
Gene lon protease
-
-
-
-
Gene lon proteins
-
-
-
-
lon
-
-
lon protease
-
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Lon proteinase
-
-
-
-
PIM1 protease
-
-
-
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PIM1 proteinase
-
-
-
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Protease La
Proteinase La
-
-
-
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Proteinase, Escherichia coli serine, La
-
-
-
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Proteinase, La
-
-
-
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Proteins, gene lon
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-
-
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Proteins, specific or class, gene lon
-
-
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Serine protease La
-
-
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Protease La
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolysis of proteins in presence of ATP
proteolysis mechanism, overview
hydrolysis of proteins in presence of ATP
hydrolysis of proteins in presence of ATP, mechanism
-
hydrolysis of proteins in presence of ATP
binding of ATP induces a conformational change that facilitates the coupling of nucleotide hydrolysis with peptide substrate delivery to the peptidase activs site
-
hydrolysis of proteins in presence of ATP
pre-steady state kinetic characterization. ATP hydrolysis occurs before peptide cleavage, with the former displaying a burst and the latter displaying a lag in the product production. ATP hydrolysis is used to generate an active enzyme that hydrolyzes peptide
-
hydrolysis of proteins in presence of ATP
presence of a catalytic Ser-Lys dyad. Definition of two enzyme subfamilies LonA and LonB, based on the consensus sequences in the active site of the proteolytic domain
-
hydrolysis of proteins in presence of ATP
reaction may involve a substrate translocation step limiting the turnover rate
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CAS REGISTRY NUMBER
COMMENTARY
79818-35-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CysD + H2O
?
a subunit of the sulfate adenylyltransferase, low activity
-
-
?
ThiS-YbeA + H2O
?
YbeA is a alpha/beta-knot methyltransferase from Escherichia coli and a deeply 31-knotted protein. Knotted fusion protein ThiS-YbeA is degraded by ClpXP. Process modeling, overview
-
-
?
ThiS-YbeA-ssrA + H2O
?
low activity, process modeling, overview
-
-
?
UCH-L1-ssrA + H2O
?
ssrA-fusion protein, UCH-L1 is a 52-knotted protein, high activity. In degradation of UCH-L1-ssrA, the degron is located at the C-terminus of the knotted protein. C-terminally tagged UCH-L1-ssrA is not noticeably degraded by ClpXP, while N-terminally tagged ssrA-x-UCH-L1 is degraded by ClpXP. The fact that the C-terminal ssrA-tag is attached directly to beta-strand 6, which is located at the centre of the core beta-sheet structure, may explain the resistance of UCH-L1-ssrA to ClpXP-induced degradation. Mutant UCH-L1-ssrA F162A is stabilised by the mutation, mutant UCH-L1-ssrA F165A is very destabilised
-
-
?
YbeA-ssrA + H2O
?
YbeA is a alpha/beta-knot methyltransferase from Escherichia coli and a deeply 31-knotted protein. Dimeric YbeA-ssrA (ssrA-tagged fusion protein of YbeA) is degraded rapidly by ClpXP, the rate of ATP-hydrolysis by ClpXP is moderately stimulated during the degradation process. Process modeling, overview
-
-
?
acid resistance regulator GdE protein + H2O
?
-
degradation of GadE protein by Lon rapidly terminates the acid resistance response upon shift back to neutral pH and avoids overexpression of acid resistance genes in stationary phases
-
-
?
beta-galactosidase fragment 3-93 + H2O
?
-
a 48-residue N-terminal variant and a 33-residue C-terminal variant of beta-galactosidase fragment are degraded very slowly. Lon rapidly degrades a variant containing the 68 N-terminal residues and a variant containing the C-terminal 43 residues of the 3-93 fragment. Residues 49-68, QLRSLNGEWRFAWFPAPEAV play an important role in regocnition by Lon
-
-
?
CNBr-fragments of bovine serum albumin + H2O
?
-
less dependent on ATP hydrolysis
-
-
?
CspD + H2O
?
-
CspD is a replication inhibitor, which is induced in stationary phase or upon carbon starvation and increases the production of persister cells. CspD is subject to proteolysis by the Lon protease both in vivo and in vitro. Turnover of CspD by Lon is strictly adjusted to the growth rate and growth phase of Escherichia coli, reflecting the necessity to control CspD levels according to the physiological conditions. Truncation or point mutation of CspD does not elevate protein stability
-
-
?
Denatured bovine serum albumin + H2O
?
-
-
-
-
?
Denatured lambda Cro protein + H2O
?
-
poor substrate, inhibits casein hydrolysis
-
-
?
DNA-binding protein HUbeta + H2O
?
-
Lon binds to both histone-like proteins HUalpha and HUbeta, but selectively degrades only HUbeta in the presence of ATP. Preferred cleavage site is the A20-A21, followed in preference by L36-K37. Degradation of substrate mutants A20D and A20Q is more slowly. Mechanism follows at least three stages: binding of Lon with the HU protein, hydrolysis of ATP by Lon to provide energy to loosen the binding to the HU protein and to allow an induced-fit conformational change, and specific cleavage of only HUbeta
-
-
?
EYLFRHSDNELLHWM + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
F-QLRSLNGEWRFAWFPAPEAV-Q + H2O
F-QLRSLNG + EWRFAWFPAPEAV-Q
-
residues 4968 of betqa-galactosidase flanked by a fluorophore-quencher pair
-
-
?
FAKYWQAFRQYPRLQ + H2O
?
-
degraded considerably faster than the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
FRQYPRLQGGFVWDW + H2O
?
-
degraded at rates within 30% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
GFP-titinI27-sul20C + H2O
?
-
when degradation initiated at the N-terminus, the full-length substrate disappears about 10fold more rapidly than when degradation initiated at the C-terminus
-
-
?
Glutaryl-Ala-Ala-Ala-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Ala + methoxynaphthylamine
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Phe + methoxynaphthylamine
Glutaryl-Gly-Gly-Pro-methoxynaphthylamide + H2O
Glutaryl-Gly-Gly-Pro + methoxynaphthylamine
heat shock sigma factor 32 + H2O
?
-
degraded by synergistic action of lon, Clp and HflB
-
-
?
homoserine trans-succinylase + H2O
?
-
degraded by synergistic action of lon, ClpYQ, ClpXP and/or ClpAP
-
-
?
HQWRGDFQFNISRYS + H2O
?
-
degraded at rates within 30% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
human alphaA-crystallin + H2O
?
-
Lon recognizes conserved determinants in the folded alpha-crystallin domain itself
-
-
?
human alphaB-crystallin + H2O
?
-
Lon recognizes conserved determinants in the folded alpha-crystallin domain itself
-
-
?
HYPNHPLWYTLCDRY + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
IbpA + H2O
?
-
i.e. Escherichia coli small heat shock protein A. Lon degrades purified IbpA substantially more slowly than purified IbpB, which is a consequence of differences in maximal Lon degradation rates and not in substrate affinity. IbpB stimulates Lon degradation of IbpA both in vitro and in vivo. The variable N- and C-terminal tails of the Ibps contain critical determinants that control the maximal rate of Lon degradation
-
-
?
IbpB + H2O
?
-
i.e. Escherichia coli small heat shock protein B. Lon degrades purified IbpA substantially more slowly than purified IbpB, which is a consequence of differences in maximal Lon degradation rates and not in substrate affinity.The variable N- and C-terminal tails of the Ibps contain critical determinants that control the maximal rate of Lon degradation
-
-
?
LLIRGVNRHEHHPLH + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
LRAGENRLAVMVLRW + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
LTEAKHQQQFFQFRL + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
MWRMSGIFRDVSLLH + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
N-glutaryl-alanylalanylphenylalanyl-3-methoxynaphthylamide + H2O
?
-
fluorogenic petide
-
?
Pro-His-Pro-Phe-His-Leu-Leu-Val-Tyr + H2O
?
-
nonapeptide related to equine angiotensinogen
-
-
?
QLRSLNGEWRFAWFPAPEAV + H2O
QLRSLNG + EWRFAWFPAPEAV
-
variant of the I27 domain of human titin containing aspartic acids in place of both wild-type cysteines and fused with residues 49-68 of beta-galactosidase fragment 3-93
-
-
?
RMVQRDRNHPSVIIW + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
RWDLPLSDMYTPYVF + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
RWLPAMSERVTRMVQ + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
RWQFNRQSGFLSQMW + H2O
?
-
degraded considerably faster than the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
S1 peptide + H2O
?
-
decapeptide S1 containing the amino acid residues 89-98 of the bacteriophage lambdaN transcription anti-termination factor, and a fluorescence donor-acceptor pair
-
-
?
Succinyl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Ala-Ala-Phe + methoxynaphthylamine
Succinyl-Phe-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Phe-Ala-Phe + methoxynaphthylamine
titin-I27CD + H2O
?
-
variant of the I27 domain of human titin containing aspartic acids in place of both wild-type cysteines
-
-
?
transcription activator SoxS + H2O
?
-
fusion of the C-terminal domain of Rob, which is a transcription activator of the SoxRS/MarA/Rob regulon, to SoxS protects its N-terminus from Lon protease, as Lon's normally rapid degradation of SoxS is blocked in the chimera
-
-
?
Unfolded polypeptides + H2O
short peptides of 5-15 amino acids
-
broad specificity
-
?
YLEDQDMWRMSGIFR + H2O
?
-
degraded at rates within 50% of the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
YWQAFRQYPRLQGGF + H2O
?
-
degraded considerably faster than the F-QLRSLNGEWRFAWFPAPEAV-Q peptide
-
-
?
MetR + H2O
?
a protein of the MetR regulon, transcriptional regulator of metE expression
-
-
?
apoTorA + H2O
?
-
a molybdoenzyme; immature TorA (apoTorA) is degraded in vivo and in vitro by the Lon protease. Enzyme Lon interacts with apoTorA but not with holoTorA. Enzyme Lon and TorD, the specific chaperone of TorA, compete for apoTorA binding, but TorD binding protects apoTorA against degradation
-
-
?
apoTorA + H2O
?
-
a molybdoenzyme, immature TorA (apoTorA) is degraded in vivo and in vitro by the Lon protease. Enzyme Lon interacts with apoTorA but not with holoTorA. Enzyme Lon and TorD, the specific chaperone of TorA, compete for apoTorA binding, but TorD binding protects apoTorA against degradation
-
-
?
ATP + H2O
phosphate + ADP
-
high-affinity sites hydrolyze ATP very slowly, but support multiple rounds of peptide hydrolysis, while the low-affinity sites hydrolyze ATP quickly. Affinities of sites differ from one another 10fold. Hydrolysis at both the high- and low-affinity sites are necessary for optimal peptide cleavage and the stabilization of the conformational change associated with nucleotide binding
-
-
?
Bacteriophage lambda protein N + H2O
Hydrolyzed bacteriophage lambda protein N
-
-
-
-
?
Bacteriophage lambda protein N + H2O
Hydrolyzed bacteriophage lambda protein N
-
cleavage sites: Ala16-Gln, Ala-Glu, Ala-Lys, Leu-Asn, Leu-Glu, Ser-Lys, Cys-Ser
-
?
casein + H2O
?
-
lon contains three distinct domains, an amino-terminal domain having an undefined function, a central ATPase domain crucial for substrate binding and unfolding, and a C-terminal peptidase domain
-
-
?
casein + H2O
hydrolyzed casein
-
alpha-casein
-
-
?
casein + H2O
hydrolyzed casein
-
methylcasein
-
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
cleavage sites: Leu6-Cys(SO3H), Leu17-Val, Ala14-Leu, Val18-Cys(SO3H)
-
?
Glutaryl-Ala-Ala-Ala-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Ala + methoxynaphthylamine
-
hydrolyzed at 3-4% the rate of glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
-
?
Glutaryl-Ala-Ala-Ala-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Ala + methoxynaphthylamine
-
hydrolyzed at 3-4% the rate of glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
?
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Phe + methoxynaphthylamine
-
-
-
?
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Phe + methoxynaphthylamine
-
-
-
-
?
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Phe + methoxynaphthylamine
-
-
-
?
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Phe + methoxynaphthylamine
-
-
-
-
?
Glutaryl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Glutaryl-Ala-Ala-Phe + methoxynaphthylamine
-
fluorogenic peptide, 0.3 mM
-
-
?
Glutaryl-Gly-Gly-Pro-methoxynaphthylamide + H2O
Glutaryl-Gly-Gly-Pro + methoxynaphthylamine
-
hydrolyzed at 6% the rate of glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
-
?
Glutaryl-Gly-Gly-Pro-methoxynaphthylamide + H2O
Glutaryl-Gly-Gly-Pro + methoxynaphthylamine
-
hydrolyzed at 6% the rate of glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
?
lambda phage N protein + H2O
?
-
generation of a panel of fluorescent peptides based on the cleavage profile of substrate lambda phage N protein indicates that protease Lon recognizes numerous discontinouos substrate determinants throughout lambda N protein to achieve substrate promiscuity
-
-
?
mDHFR protein + H2O
?
-
tittinI27-fusion and sul20C-tagged protein, to direct Lon degradation of a titinI27 domain, either the N or C terminus of this protein is fused to amino acids 3-93 of Escherichia coli beta-galactosidase, an unstructured sequence that contains the b20 degron, degradation
-
-
?
Melittin + H2O
?
-
isolated proteolytic domain exhibits almost no activity toward casein, but hydrolyzes peptide substrates
-
?
Oxidized insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
cleavage sites
-
?
Oxidized insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
cleavage sites
-
-
?
Proteins with highly abnormal conformation + H2O
?
-
one of the heat-shock proteins under control of rpoH operon(htp R)
-
-
?
Proteins with highly abnormal conformation + H2O
?
-
rate-limiting step in breakdown of highly abnormal and some normal proteins
-
-
?
Proteins with highly abnormal conformation + H2O
?
-
catalyzes inital step in the degradation of proteins with abnormal conformation as may result from nonsense or missense mutations, biosynthetic errors or intracellular denaturation
-
-
?
RcsA + H2O
?
-
protein degradation mediates the turnover of damaged proteins
-
?
ribosomal S2 protein + H2O
?
-
degradation of S2 protein occurs in a processive manner. P1 and P3 sites of cleavage products are predominantly occupied by hydrophobic residues
-
-
?
ribosomal S2 protein + H2O
?
-
major lon cleavages sites within the bacterial S2 ribosomal protein located at the interior of the molecule
-
-
?
Succinyl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Ala-Ala-Phe + methoxynaphthylamine
-
best substrate
-
-
?
Succinyl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Ala-Ala-Phe + methoxynaphthylamine
-
best substrate
-
?
Succinyl-Ala-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Ala-Ala-Phe + methoxynaphthylamine
-
hydrolyzed at 137% the rate of glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
?
Succinyl-Phe-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Phe-Ala-Phe + methoxynaphthylamine
-
-
-
?
Succinyl-Phe-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Phe-Ala-Phe + methoxynaphthylamine
-
-
-
-
?
Succinyl-Phe-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Phe-Ala-Phe + methoxynaphthylamine
-
-
-
?
Succinyl-Phe-Ala-Phe-methoxynaphthylamide + H2O
Succinyl-Phe-Ala-Phe + methoxynaphthylamine
-
fluorogenic peptide, hydrolyzed at 75% the rate of glutaryl-Ala-Ala-Phe-methoxynaphthylamide
-
-
?
SulA + H2O
?
-
inactivation of SulA through the enzyme in vivo requires binding to the N domain and robust ATP hydrolysis but does not require degradation or translocation into the proteolytic chamber
-
-
?
tmRNA-tagged protein + H2O
?
-
highly purified lon preferentially degrades tmRNA-tagged forms of proteins compared to untagged forms
-
-
?
additional information
?
-
a quantitative Super-SILAC (stable isotope labeling with amino acids in cell culture) mass spectrometry approach and analysis of proteomes of a lon mutant and a strain producing the protease are employed to determine substrate specificity and Lon-dependent physiological functions. The recognition mechanisms of known Lon substrates are highly diverse. Misfolded proteins are mainly recognized by short, hydrophobic stretches normally buried in the core of natively folded proteins. In contrast, recognition of SulA occurs via its C-terminus with a critical histidine and tyrosine at its very end
-
-
?
additional information
?
-
-
a quantitative Super-SILAC (stable isotope labeling with amino acids in cell culture) mass spectrometry approach and analysis of proteomes of a lon mutant and a strain producing the protease are employed to determine substrate specificity and Lon-dependent physiological functions. The recognition mechanisms of known Lon substrates are highly diverse. Misfolded proteins are mainly recognized by short, hydrophobic stretches normally buried in the core of natively folded proteins. In contrast, recognition of SulA occurs via its C-terminus with a critical histidine and tyrosine at its very end
-
-
?
additional information
?
-
Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities
-
-
?
additional information
?
-
enzyme Ec-Lon interacts with DNA. Ec-Lon protease forms complexes with aptamers, obtained from thrombin, whose molecules comprise the duplex domains and G-quadruplex region. The aptamers have low affinities for the enzyme mutant S679A, the Lon protease does not show a strong ability to bind to any individual Gx02quadruplex (15TBA) or duplex aptamer (RE15T), but Lonx02 S679A forms complexes with twox02domain 31TBA, RE31 and ST43 aptamers
-
-
?
additional information
?
-
Lon protease has three activities: intrinsic ATPase, substrate-stimulated ATPase, and ATP-dependent proteolysis. Lon preferentially degrades damaged or misfolded proteins at its proteolytic site while the ATP is bound and hydrolyzed into ADP and phosphate at its ATPase site
-
-
?
additional information
?
-
-
Lon protease has three activities: intrinsic ATPase, substrate-stimulated ATPase, and ATP-dependent proteolysis. Lon preferentially degrades damaged or misfolded proteins at its proteolytic site while the ATP is bound and hydrolyzed into ADP and phosphate at its ATPase site
-
-
?
additional information
?
-
N-terminally truncated enzyme ClpXP can easily degrade a deeply 31-knotted and 52-knotted proteins. The degradation depends critically on the location of the degradation tag and the local stability near the tag
-
-
?
additional information
?
-
the enzyme is able to undergo autolysis and to bind DNA, analysis of formation of enzyme-DNA complexes
-
-
?
additional information
?
-
-
the enzyme is able to undergo autolysis and to bind DNA, analysis of formation of enzyme-DNA complexes
-
-
?
additional information
?
-
-
No substrates are native bovine serum albumin, hemoglobin
-
-
?
additional information
?
-
-
No substrates are native bovine serum albumin, hemoglobin
-
-
?
additional information
?
-
-
No substrates are glutaryl-Phe-7-amino-4-methylcoumarin, Ala-Ala-Phe-methoxynaphthylamide, Gly-Phe-methoxynaphthylamide, Asp-methoxynaphthylamide, Leu-methoxynaphthylamide, Arg-methoxynaphthylamide, Ala-methoxynaphthylamide, Tyr-methoxynaphthylamide, Lys-methoxynaphthylamide, methoxyglutaryl-Ala-Ala-Phe-methoxynaphthylamide, methoxysuccinyl-Ala-Ala-Phe-methoxynaphthylamide, benzyloxycarbonyl-Ala-Pro-methoxynaphthylamide, benzoyl-Arg-Gly-Phe-Phe-Leu-methoxynaphthylamide, benzoyl-Arg-Gly-Leu-methoxynaphthylamide, Leu-Gly-Gly-methoxynaphthylamide, Ser-Tyr-methoxynaphthylamide
-
-
?
additional information
?
-
-
No substrates are lambda-repressors cI and Cro, lambda replication protein O, E. coli galactose repressor, even after heat denaturation
-
-
?
additional information
?
-
-
the active site prefers hydrophobic substrate sequences
-
-
?
additional information
?
-
-
mutant enzyme in which active site Ser-679 is replaced by Ala lacks peptidase but retains ATPase activity
-
-
?
additional information
?
-
-
no phosphorylation of enzyme or substrate during ATP hydrolysis
-
-
?
additional information
?
-
-
with a proteolytic and an ATP-binding site per monomer
-
-
?
additional information
?
-
-
No substrates are benzyloxycarbonyl-Ala-Arg-Arg-methoxynaphthylamide, native or denatured ribonuclease, native or denatured lysozyme, native immunoglobulin G
-
-
?
additional information
?
-
-
can bind to a TG-rich DNA promoter element in a sequence-specific manner
-
?
additional information
?
-
-
isolated proteolytic domain exhibits the peptidase activity
-
?
additional information
?
-
-
essential for growth of yeast on nonfermentable carbon sources
-
-
?
additional information
?
-
-
rapid proteolysis plays a major role in post-translational cellular control by the targeted degradation of short-lived regulatory proteins
-
?
additional information
?
-
-
recognition and selective degradation of abnormal and unstable proteins
-
?
additional information
?
-
-
regulation of several important cellular functions, including radiation resistance, cell division, filamentation, capsular polysaccharide production, lysogeny of certain bacteriophages, and proteolytic degradation of certain regulatory and abnormal proteins
-
?
additional information
?
-
-
enzyme and protease Clp participate in the physiological disintegration of cytoplasmic inclusion bodies, their absence minimizing the protein removal up to 40%. Clp takes the major and enzyme a minor role in processing of aggregation-prone proteins and also of polypeptides physiologically released from inclusion bodies
-
-
?
additional information
?
-
-
the polyphosphate-lon complex does not degrade intact native ribosomes
-
-
?
additional information
?
-
-
proteolytic domain and a a large N-terminal domain, active site has a Ser-Lys catalytic dyad. Proteolytic domain exhibits no detectable activity against protein substrates degraded by full-length lon, but retains a significant fraction of peptidase activity
-
-
?
additional information
?
-
-
protease Lon recognizes specific sequences rich in aromatic residues that are accessible in unfolded polypeptides but hidden in most native structures. Denatured polypeptides lacking such sequences are poor substrates. Lon also unfolds and degrades stably folded proteins with accessible recognition tags. Lon can recognize multiple signals in unfolded polypeptides synergistically, resulting in nanomolar binding and a mechanism for discriminating irreversibly damaged proteins from transiently unfolded elements of structure
-
-
?
additional information
?
-
-
enzyme recognizes degrons, i.e. degradation tags. Degron tags are also regulatory elements that determine protease activity levels. Different tags fused to the same protein change degradation speeds and energetic efficiencies by 10fold or more. Degron binding to multiple sites in the Lon hexamer differentially stabilizes specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation
-
-
?
additional information
?
-
-
Lon possesses an intrinsic ATPase activity that is stimulated by protein and certain peptide substrates. The ATPase reaction catalyzed by Lon in the presence and absence of peptide substrate that stimulates the enzyme's ATPase activity is irreversible. The half-site ATPase reactivity of Lon can be used to account for the kinetic mechanism of the ATP-dependent peptidase activity of the enzyme
-
-
?
additional information
?
-
-
the alpha-domain from Lon binds to the duplex nucleotide sequence 5'-CTGTTAGCGGGC-3' from pET28a plasmid DNA sequence map and protects it from DNase I digestion. The Brevibacillus thermoruber Lon alpha-domain binds with 5'-CTGTTAGCGGGC-3' double-stranded DNA tighter than Lon alpha-domains from Escherichia coli and Bacillus subtilis, whereas the Brevibacillus thermoruber Lon alpha-domain has dramatically lower affinity for double-stranded DNA with 0 and 50% identity to the 5'-CTGTTAGCGGGC-3' binding sequence
-
-
?
additional information
?
-
-
homooligomeric ATP-dependent LonA proteases are bifunctional enzymes
-
-
?
additional information
?
-
-
repeated cycles of ATP binding and hydrolysis power conformational changes that pull the tag through the pore and eventually tug the native portion of the substrate against the AAA+ ring, creating an unfolding force. Depending on the native substrate and enzyme, successful unfolding can require anywhere from a few to many hundreds of cycles of ATP hydrolysis
-
-
?
additional information
?
-
-
compared with hexamers, enzyme dodecamers are much less active in degrading large substrates but equally active in degrading small substrates, whcih represents a a unique gating mechanism that allows the repertoire of enzyme substrates to be tuned by its assembly state
-
-
?
additional information
?
-
-
native enzyme hydrolyzes ATP in the absence of a protein substrate
-
-
?
additional information
?
-
-
substrate specifiicty, overview. GFP-fusion proteins resist Lon degradation from the N-terminus. Partially degraded substrate fragments accumulate as proteolytic products, which is often observed during degradation in vitro of multi-domain substrates containing very stable interior domains
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CysD + H2O
?
a subunit of the sulfate adenylyltransferase, low activity
-
-
?
MetR + H2O
?
a protein of the MetR regulon, transcriptional regulator of metE expression
-
-
?
acid resistance regulator GdE protein + H2O
?
-
degradation of GadE protein by Lon rapidly terminates the acid resistance response upon shift back to neutral pH and avoids overexpression of acid resistance genes in stationary phases
-
-
?
apoTorA + H2O
?
-
a molybdoenzyme; immature TorA (apoTorA) is degraded in vivo and in vitro by the Lon protease. Enzyme Lon interacts with apoTorA but not with holoTorA. Enzyme Lon and TorD, the specific chaperone of TorA, compete for apoTorA binding, but TorD binding protects apoTorA against degradation
-
-
?
Proteins with highly abnormal conformation + H2O
?
-
one of the heat-shock proteins under control of rpoH operon(htp R)
-
-
?
Proteins with highly abnormal conformation + H2O
?
-
rate-limiting step in breakdown of highly abnormal and some normal proteins
-
-
?
Proteins with highly abnormal conformation + H2O
?
-
catalyzes inital step in the degradation of proteins with abnormal conformation as may result from nonsense or missense mutations, biosynthetic errors or intracellular denaturation
-
-
?
RcsA + H2O
?
-
protein degradation mediates the turnover of damaged proteins
-
?
SulA + H2O
?
-
inactivation of SulA through the enzyme in vivo requires binding to the N domain and robust ATP hydrolysis but does not require degradation or translocation into the proteolytic chamber
-
-
?
additional information
?
-
a quantitative Super-SILAC (stable isotope labeling with amino acids in cell culture) mass spectrometry approach and analysis of proteomes of a lon mutant and a strain producing the protease are employed to determine substrate specificity and Lon-dependent physiological functions. The recognition mechanisms of known Lon substrates are highly diverse. Misfolded proteins are mainly recognized by short, hydrophobic stretches normally buried in the core of natively folded proteins. In contrast, recognition of SulA occurs via its C-terminus with a critical histidine and tyrosine at its very end
-
-
?
additional information
?
-
-
a quantitative Super-SILAC (stable isotope labeling with amino acids in cell culture) mass spectrometry approach and analysis of proteomes of a lon mutant and a strain producing the protease are employed to determine substrate specificity and Lon-dependent physiological functions. The recognition mechanisms of known Lon substrates are highly diverse. Misfolded proteins are mainly recognized by short, hydrophobic stretches normally buried in the core of natively folded proteins. In contrast, recognition of SulA occurs via its C-terminus with a critical histidine and tyrosine at its very end
-
-
?
additional information
?
-
Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities
-
-
?
additional information
?
-
-
essential for growth of yeast on nonfermentable carbon sources
-
-
?
additional information
?
-
-
rapid proteolysis plays a major role in post-translational cellular control by the targeted degradation of short-lived regulatory proteins
-
?
additional information
?
-
-
recognition and selective degradation of abnormal and unstable proteins
-
?
additional information
?
-
-
regulation of several important cellular functions, including radiation resistance, cell division, filamentation, capsular polysaccharide production, lysogeny of certain bacteriophages, and proteolytic degradation of certain regulatory and abnormal proteins
-
?
additional information
?
-
-
enzyme and protease Clp participate in the physiological disintegration of cytoplasmic inclusion bodies, their absence minimizing the protein removal up to 40%. Clp takes the major and enzyme a minor role in processing of aggregation-prone proteins and also of polypeptides physiologically released from inclusion bodies
-
-
?
additional information
?
-
-
the polyphosphate-lon complex does not degrade intact native ribosomes
-
-
?
additional information
?
-
-
protease Lon recognizes specific sequences rich in aromatic residues that are accessible in unfolded polypeptides but hidden in most native structures. Denatured polypeptides lacking such sequences are poor substrates. Lon also unfolds and degrades stably folded proteins with accessible recognition tags. Lon can recognize multiple signals in unfolded polypeptides synergistically, resulting in nanomolar binding and a mechanism for discriminating irreversibly damaged proteins from transiently unfolded elements of structure
-
-
?
additional information
?
-
-
homooligomeric ATP-dependent LonA proteases are bifunctional enzymes
-
-
?
additional information
?
-
-
repeated cycles of ATP binding and hydrolysis power conformational changes that pull the tag through the pore and eventually tug the native portion of the substrate against the AAA+ ring, creating an unfolding force. Depending on the native substrate and enzyme, successful unfolding can require anywhere from a few to many hundreds of cycles of ATP hydrolysis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
ClpXP is a ATP-dependent protease. ClpXP displays a basal rate of ATP hydrolysis even when not engaged in protein degradation and in the presence of ssrA-tagged substrate PR65/A, although not with UCH-L1-ssrA, the ATPase rate is stimulated
ATP
-
requirement
ATP
-
enzyme tetramer has two high and two low affinity binding sites for ATP
ATP
-
proteolytically inactive mutant enzyme with completely unaffected ATPase activity
ATP
-
two ATP molecules are hydrolyzed for each peptide bond cleaved in proteins
ATP
-
binds to enzyme as allosteric activator allowing peptide bond hydrolysis with subsequent ATP hydrolysis
ATP
-
ATP-dependent protease
29339, 29340, 29342, 29343, 29344, 29345, 29346, 29347, 29348, 29349, 29350, 29351, 29352, 29353, 29354, 29356, 29357, 29358, 29359, 29360, 29361
ATP
-
enzyme binds 4 mol ATP per tetramer at ATP concentrations above 0.01 mM
ATP
-
enzyme binds 2 mol ATP/tetramer in the absence of divalent cations or at 0.01 mM ATP in the presence of Mn2+ or Mg2+
ATP
-
diphosphate, adenyl-5'-yl methylene diphosphate, GTP, UTP and CTP at 1 mM have no effect on the binding of ATP to the enzyme
ATP
-
binding of ATP induces a conformational change that facilitates the coupling of nucleotide hydrolysis with peptide substrate delivery to the peptidase active site
ATP
-
optimal peptide cleavage by lon requires hydrolysis of ATP to fully activate the proteolytic site
ATP
-
required, protein degradation by Lon is dependent on energy obtained from ATP hydrolysis, modelng of the structure of hexameric ATPase domain of EcLon protease using the comparative modeling approach, overview
CTP
-
hydrolysis at 82% the rate of ATP, supports proteolysis with 31% the efficiency of ATP
UTP
-
hydrolysis at 77% the rate of ATP, supports proteolysis with 22% the efficiency of ATP
additional information
replacement of ATP by its non-hydrolyzable analogue (AMP-PNP) leads to a marked decrease in the substrate transformation rate and a change of the mechanism of casein hydrolysis for nonprocessive
-
additional information
-
adenylyl 5-imidodiphosphate, can replace ATP, shows a reduced peptidase activity
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Ca2+
diphosphate
Mg2+
Mn2+
Tetraphosphate
-
activation, only peptide hydrolysis, in the presence of Mg2+
Triphosphate
Mg2+
required, activates, but excess of magnesium ions has an inhibitory effect on the hydrolysis of ATP
Ca2+
-
with equal efficiency in peptide hydrolysis (not protein hydrolysis)
diphosphate
-
in the presence of Mg2+, only peptide hydrolysis, not casein or serum albumin hydrolysis
Mg2+
-
requirement
Mg2+
-
required for maximal ATP-binding and essential for proteolytic activity
Mg2+
-
in absence, dissociation into monomers and/or dimers. In presence of Mg2+, strong and ATP-independent tendency to form hexamers
Mg2+
-
activates, presence of free Mg2+ ions inhibits the ATPase activity of the enzyme, the effect is eliminated in the presence of the protein substrate
Triphosphate
-
only peptide hydrolysis, not casein or serum albumin hydrolysis
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mg2+
excess of magnesium ions has an inhibitory effect on the hydrolysis of ATP
2',3'-dialdehyde-ATP
-
i.e. adenosine 2',3'-dialdehyde triphosphate, in the presence of ATP, globin as substrate
adenosine 5'-(3-thiotriphosphate)
-
i.e. ATP-gamma-S, in the presence of ATP, globin as substrate
Benzoyl-Arg-Gly-Phe-Phe-Leu-methoxynaphthylamide
-
glutaryl-Ala-Ala-Phe-methoxynaphthylamide or casein as substrate
cardiolipin
-
cardiolipin-containing liposomes specifically inhibit both the proteolytic and ATPase activities of Lon in a dose-dependent manner. Cardiolipin-containing liposomes selectively bind to Lon. The interaction between cardiolipin-containing liposomes and Lon changes with the order of addition of Mg2+/ATP. When cardiolipin-containing liposomes are added after the addition of Mg2+/ATP to Lon, the binding of cardiolipin-containing liposomes to Lon is significantly decreased as compared with the reversed order
Peptide substrates
-
inhibit ATP hydrolysis, protein substrates promote ATP hydrolysis
-
Protein R9 from Escherichia coli mutant strain capR9
-
protein, peptide and ATP hydrolysis
-
TorD
-
impairs the enzyme's TorA degradation activity by binding to apoTorA
-
ADP
free ADP inhibits all forms of Ec-Lon, while a complex of ADP with magnesium ions (ADP-Mg) activates C-His-Lon and Lon-R164A and inhibits the mutant forms Lon R192A and Lon-Y294A
ADP
non-competitive inhibition, ELon binds to ADP and undergoes at least one structural change that exposes a tryptic digestion site
bacteriophage T4 PinA protein
-
inhibits degradation of alpha-methyl-casein and CcdA, noncompetitive inhibition, no inhibition of cleavage of N-glutaryl-alanylalanylphenylalanyl-3-methoxynaphthylamide
-
bacteriophage T4 PinA protein
-
specifically inhibits Escherichia coli Lon
-
Polyphosphate
-
competitively blocks DNA binding by lon in vitro and in vivo
Polyphosphate
-
slightly inhibits degradation of a maltose-binding protein-SulA fusion. At the ATP domain competes with DNA for binding to lon, completely inhibits the formation of a DNA-lon complex
tosyl-Lys chloromethyl ketone
-
weak, casein as substrate, no inhibition with glutaryl-Ala-Ala-Phe methoxynaphthylamide as substrate
additional information
-
high-affinity site of lon can be blocked with unlabeled nucleotide, conformational change associated with nucleotide binding
-
additional information
-
inhibition of activity by the T4-encoded PinA protein, non-competetive inhibitor
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DNA
Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities
Adenosine 2',3'-dialdehyde triphosphate
-
activation, hydrolysis at 23% the rate of ATP, supports proteolysis with 30% the efficiency of ATP
Adenosine 5'-(alpha-thio)triphosphate
-
activation, Rp-diastereoisomer stimulates peptide hydrolysis much more effectively than Sp-diastereoisomer
adenyl-5'-yl methylene monophosphonate
-
i.e. AMP-CPP, activation, competes for the two ATP-high affinity sites
Bovine glucagon
-
activation, glutaryl-Ala-Ala-Phe methoxynaphthylamide hydrolysis, with or without ATP, not casein hydrolysis
degron
-
degron binding to this site is not required for proteolysis of sul20-tagged substrates in vitro but enhances degradation by allosterically activating protease activity. Sul20 degron from the cell-division inhibitor SulA binds to the N domain of the enzyme, determination of the recognition site, overview. Allosteric role for the sul20-binding site in the N domain
-
Denatured calf thymus or E. coli DNA
-
stimulation of glutaryl-Ala-Ala-Phe-methoxynaphthylamide hydrolysis
-
spermidine
-
activation, at physiological concentration, ATP hydrolysis and protease activity
adenosine 5'-(3-thiotriphosphate)
-
i.e. adenosine 5'-O-(thiotriphosphate) or ATP-gamma-S, activation
adenosine 5'-(3-thiotriphosphate)
-
equally effective as ATP with casein as substrate
adenosine 5'-(3-thiotriphosphate)
-
hydrolysis, peptide not protein hydrolysis
adenosine 5'-(3-thiotriphosphate)
-
activates, hydrolysis of casein or glutaryl-Ala-Ala-Phe-methoxynaphthylamide
Adenyl-5'-yl imidodiphosphate
-
casein or glutaryl-Ala-Ala-Phe-methoxynaphthylamide hydrolysis
Adenyl-5'-yl imidodiphosphate
-
i.e. AMP-PNP, activation
Adenyl-5'-yl imidodiphosphate
-
competes for one of the ATP-high-affinity binding-sites
Adenyl-5'-yl imidodiphosphate
-
no activation of bovine serum albumin hydrolysis
adenyl-5'-yl methylene diphosphonate
-
i.e. AMP-PCP, activation
adenyl-5'-yl methylene diphosphonate
-
casein or glutaryl-Ala-Ala-Phe-methoxynaphthylamide hydrolysis
casein
-
activation, glutaryl-Ala-Ala-Phe-methoxynaphthylamide or insulin B-chain hydrolysis, in the absence of ATP and synergistic with ATP
Denatured bovine serum albumin
-
glutaryl-Ala-Ala-Phe methoxynaphthylamide hydrolysis, with or without ATP
-
GTP
-
hydrolysis at 113% the rate of ATP, supports proteolysis with 14% the efficiency of ATP
Polyphosphate
-
changes substrate preference of enzyme and its oligomeric structure
Polyphosphate
-
upon binding to a site in the ATPase domain, stimulation of degradation of ribosomal protein and inhibition of DNA-enzyme complex formation
Polyphosphate
-
forms a complex with lon, which enables lon to degrade free ribosomal proteins. Polyphosphate with a shorter chain length is less potent in stimulating. Polyphosphate-binding site is within the ATPase domain fo lon between amino acids 320 and 437
Polyphosphate
-
its binding within the ATPase domain of lon promotes the specific association and degradation of free ribosomal proteins
Polyphosphate
-
stimulates lon proteolytic activity, affects substrate preference and oligomeric state of the enzyme
Polyphosphate
-
stimulates lon-mediated proteolysis of free ribosomal proteins and thereby down-regulates translation
Protein substrates
-
stimulation of ATP hydrolysis triggers activation of the proteolytic function
-
Protein substrates
-
rise in ATPase activity proportional to peptide bonds cleaved
-
Protein substrates
-
protein substrates, e.g. denatured bovine serum albumin induce ADP-release and promote ATP-ADP-exchange
-
Protein substrates
-
protein substrates enhance additively the stimulating effect of ATP on peptide hydrolysis and even in the absence of ATP they enhance the ability to degrade fluorogenic tripeptides
-
additional information
-
enzyme hydroylzes proteins and ATP in a coupled process
-
additional information
-
enzyme hydroylzes proteins and ATP in a coupled process
-
additional information
-
peptide substrates, e.g. glutaryl-Ala-Phe-Phe methoxynaphthylamide or succinyl-Phe-Leu-Phe methoxynaphthylamide do not support ATP hydrolysis
-
additional information
-
no activation by benzoyl-Arg-Gly-Phe-Phe-Leu methoxynaphthylamide (glutaryl-Ala-Ala-Phe methoxynaphthylamide as substrate), poly(A)
-
additional information
-
no activation by nonhydrolyzable proteins, e.g. native or denatured ribonuclease or lysozyme
-
additional information
-
nonhydrolyzable ATP-analogs are much less effective than ATP in supporting hydrolysis of large proteins
-
additional information
-
protein degradation requires nucleoside triphosphate hydrolysis, cleavage of small peptides only requires binding of nucleotides to the enzyme
-
additional information
-
ATP cannot be replaced by adenosine 5'-(beta-thiotriphosphate)
-
additional information
-
degradation of proteins stimulates ATPase activity of lon
-
additional information
-
the enzyme activity of Lon can be stimulated by the presence of unfolded proteins (e.g. apomyoglobin, glucagon, and alpha-casein) as well as inorganic polyphosphate accumulated during amino acid starvation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
beta-galactosidase-93-titinI27
-
pH not specified in the publication, 37°C
-
0.015
titinI27-beta-galactosidase-93
-
pH not specified in the publication, 37°C
-
0.023
titinI27-beta-galactosidase-93-titinI27
-
pH not specified in the publication, 37°C
-
additional information
additional information
Michaelis-Menten plot of YbeA-ssrA degradation
-
0.035
human alphaA-crystallin
-
substrate lacking both C- and N-terminal tail, pH 8.0, 37°C
-
0.026
human alphaB-crystallin
-
substrate lacking both C- and N-terminal tail, pH 8.0, 37°C
-
0.0022
human titin
-
unfolded, bearing a sul20C peptide variant with an N-terminal PABA fluorophoreand a nitrotyrosine quencher at the penultimate C-terminal position followed by alanine at the C-terminus of the I27 domain, pH 8.0, 37°C
-
0.024
human titin
-
unfolded, bearing a 20-residue beta-galactosidase sequence at the C-terminus of the I27 domain, pH 8.0, 37°C
-
0.04
human titin
-
native, bearing C-terminal 20 residues of SulA sequence at the C-terminus of the I27 domain, pH 8.0, 37°C
-
0.05
human titin
-
native, bearing a 20-residue beta-galactosidase sequence at the C-terminus of the I27 domain, pH 8.0, 37°C
-
0.053
human titin
-
unfolded, bearing C-terminal 20 residues of SulA sequence at the C-terminus of the I27 domain, pH 8.0, 37°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kcat-value of peptide cleavage decreases with the reduction in the nucleotide binding affinity in the following order: ATP, CTP, GTP, UTP. Both nucleotide binding and hydrolysis contribute to peptidase turnover
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000036
bacteriophage T4 PinA protein
-
pH 8.0, 25°C, inhibition of casein hydrolysis
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.1
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
37
-
assay at
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
normally localized in nucleoids. Also present in polyphosphate granules of a phoU mutant, wich accumulates polyphosphate several 100fold higher than the wild-type
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
ATP-dependent Lon protease of Escherichia coli (Ec-Lon) is a key enzyme of the quality control system of the cell proteome
physiological function
evolution
malfunction
-
deletion of Lon's ATPase domain abrogates interactions with DNA. Substitution of positively charged amino acids in this domain in full-length Lon with residues conferring a net negative charge disrupts binding of Lon to DNA. These changes also affect the degradation of nucleic acid binding protein substrates of Lon, intracellular localization of Lon, and cell morphology. The DNA-binding defect of Lon protease affects plasmid replication initiator protein TrfA proteolysis. And the Lon mutants are defective in proper cellular localization, most probably due to their impaired ability to form a nucleoprotein complex. The phenotype of the DNA binding-defective Lon mutants is similar to that observed for Lon-deficient strains
physiological function
additional information
evolution
human enzyme hLon and Escherichia coli enzyme ELon bind to ADP and undergo at least one structural change that exposes the same tryptic digestion site, suggesting the presence of at least one conserved structural change in the two enzyme homologues upon binding to ADP
evolution
Lon is a highly conserved member of the AAA+ (ATPases associated with diverse cellular activities) protease family
evolution
Lon proteases can be divided into two subfamilies: LonA (found in eubacteria and eukarya) and LonB (found in archaea). LonA proteases are formed by three functional domains: the N-terminal, involved in substrate binding, the central AAA+ domain, and the C-terminal domain (named P domain), which containing the Ser-Lys catalytic dyad for proteolytic activity. LonB proteases are composed by an ATPase and a protease domain and a hydrophobic transmembrane region which anchors the protein to the internal face of cell membrane
evolution
LonA from Escherichia coli belongs to the superfamily of AAA+ proteins, family S16 of proteases. The presence of an extended variable N-terminal region preceding the AAA+ modules is a characteristic feature of LonA proteases distinguishing them from other AAA+ proteins
evolution
the enzyme belongs to the protease family S16 and to the superfamily of AAA+ proteins
malfunction
a Lon trapping variant, which is able to translocate substrates but unable to degrade them, is established and used for substrate determinations by mass spectrometry
malfunction
removal of the HI(CC) domain results in a dexadcrease in the activity of the peptidase center of the Ec-Lon protease and a loss of the regulatory effect of the ATPase center on the peptidase one, which is defined by the nature of the bound nucleotide in the intact enxadzyme. Deletion of the HI(CC) domain leads to a complete loss of the proteolytic activity towards beta-casein by the deletion form
malfunction
the deletion form DELTArLon is incapable of hydrolyzing beta-casein in the time interval in which the proteolytic activity of full-length rLon protease is tested
malfunction
the Lon mutant variant V217A/Q220A (LonVQ) forms a dodecamer with increased stability compared to wild-type. Cells expressing only LonVQ are healthier than Lon-deficient strains during normal growth and perform similarly to wild-type Lon in a panel of in vivo bioassays except for degradation of small heat shock proteins. At 37°C, the enzyme-ddeficient DELTAlon strain grows significantly slower than the wild-type strain and never establishes a true exponential phase, but loss of Lon activity is not deleterious to viability
physiological function
a quantitative Super-SILAC (stable isotope labeling with amino acids in cell culture) mass spectrometry approach and analysis of proteomes of a lon mutant and a strain producing the protease are employed to determine substrate specificity and Lon-dependent physiological functions, Lon affected proteins, overview. Fundamental functions of Lon in sulfur assimilation, nucleotide biosynthesis, amino acid and central energy metabolism, besides the superoxide stress response function. Lon protease affects the MetR regulon and function of proteins MetE and MetR
physiological function
Lon protease is one of the main participants of the proteome quality control (PQC) system supporting normal cell homeostasis. The PQC system involves molecular chaperones participating in the remodeling and disaggregation of cellular proteins and ATP-dependent peptide hydrolases, which control the level of regulatory proteins through selective proteolysis and eliminate potentially hazardous, anomalous, defective, and redundant proteins from cells through their exhaustive degradation. All proteases of the PQC system are bifunctional enzymes whose proteolytic activity is coupled with the simultaneous ATP hydrolysis and is characterized by a processive mechanism of the hydrolysis of protein targets (without the release of high-molecular-weight intermediates)
physiological function
LonA from Escherichia coli plays a key role in the quality control system of the cell proteome. It destroys abnormal and defective polypeptides, as well as a number of regulatory proteins, according to a processive degradation mechanism
physiological function
multidomain ATP-dependent Lon protease of Escherichia coli is one of the key enzymes of the quality control system of the cellular proteome. The HI(CC) domain of Ec-Lon protease is required for the formation of a functionally active enzyme structure and for the implementation of protein-protein interactions
physiological function
the protein quality control network (pQC) plays critical roles in maintaining protein and cellular homeostasis, especially during stress. Protease Lon is one of the central proteases responsible for protein quality control (pQC). It is the principal enzyme that degrades most unfolded or damaged proteins. Degradation by Lon also controls cellular levels of several key regulatory proteins. Analysis of biological roles of the Lon dodecamer. The enzyme dodecamer successfully completes many of the Lon protease's important regulatory functions while modifying substrate choice, perhaps to better manage protein quality control under conditions such as UV, heat, and oxidative stress
physiological function
together with its proteolytic and chaperone activities, Lon ability to bind mtDNA is conserved from bacteria to mammalian mitochondria. Escherichia coli Lon binds both single stranded DNA (ssDNA) and RNA (ssRNA), and double stranded DNA (dsDNA) in a non-specific manner, and this interaction enhances Lon ATPase and proteolytic activities. Lon ability to bind to DNA needs conformational changes in Lon itself, and such changes are inhibited by ATP, and are stimulated by a protein substrate
evolution
-
evolution has diversified rather than optimized the protein unfolding activities of different AAA+ proteases, Escherichia coli utilizes five different AAA+ proteases: Lon, ClpXP, ClpAP, HslUV, and FtsH
evolution
-
homooligomeric ATP-dependent LonA proteases are bifunctional enzymes belonging to the superfamily of AAA+ proteins
physiological function
-
absence of Lon protease blocks paradoxical survival occurring at very high nalidixic acid concentrations. The absence of Lon also blocks a parallel increase in cell lysate viscosity likely to reflect DNA size
physiological function
-
Lon possesses an intrinsic ATPase activity that is stimulated by protein and certain peptide substrates. The ATPase reaction catalyzed by Lon in the presence and absence of peptide substrate that stimulates the enzyme's ATPase activity is irreversible
physiological function
-
the alpha-domain from Lon binds to the duplex nucleotide sequence 5'-CTGTTAGCGGGC-3' from pET28a plasmid DNA sequence map and protects it from DNase I digestion. The Brevibacillus thermoruber Lon alpha-domain binds with 5'-CTGTTAGCGGGC-3' double-stranded DNA tighter than Lon alpha-domains from Escherichia coli and Bacillus subtilis, whereas the Brevibacillus thermoruber Lon alpha-domain has dramatically lower affinity for double-stranded DNA with 0 and 50% identity to the 5'-CTGTTAGCGGGC-3' binding sequence
physiological function
-
the Lon protease and the SecB and DnaJ/Hsp40 chaperones are involved in the quality control of presecretory proteins in Escherichia coli. Mutations in the lon gene alleviate the cold-sensitive phenotype of a secB mutant. In comparison to the respective single mutants, the double secB lon mutant strongly accumulates aggregates of SecB substrates at physiological temperatures, suggesting that the chaperone and the protease share substrates. The main substrates identified in secB lon aggregates, namely proOmpF and proOmpC, are highly sensitive to specific degradation by Lon. In contrast, both substrates are significantly protected from Lon degradation by SecB. The chaperone DnaJ by itself protects substrates better from Lon degradation than SecB or the complete DnaK/DnaJ/GrpE chaperone machinery
physiological function
-
transposon inactivation of ycgE, encoding a putative transcriptional regulator, leads to decreased multidrug susceptibility in an Escherichia coli lon mutant. The multidrug susceptibility phenotype e.g., to tetracycline and beta-lactam antibiotics, requires the inactivation of both lon and ycgE. In this mutant, a decreased amount of OmpF porin contributes to the lowered drug susceptibility, with a greater effect at 26°C than at 37°C
physiological function
-
AAA+ proteases employ a hexameric ring that harnesses the energy of ATP binding and hydrolysis to unfold native substrates and translocate the unfolded polypeptide into an interior compartment for degradation. Ability of theLon protease to unfold and degrade model protein substrates beginning at N-terminal, C-terminal, or internal degrons, unfolding with robust and processive unfolding/degradation of some substrates with very stable protein domains, including mDHFR and titin, overview
physiological function
-
Lon is an ATPase associated with cellular activities protease that controls cell division in response to stress and also degrades misfolded and damaged proteins
physiological function
-
protease Lon eliminates an immature or misfolded molybdoenzyme probably by targeting its inactive catalytic site, it is involved in the apoTorA degradation process
physiological function
-
the ATP-dependent Lon protease is a key component of the quality control system, which ensures the integrity and functionality of cellular proteins
physiological function
-
the enzyme can function as a protease or a chaperone and reveal that some of its ATP-dependent biological activities do not require translocation. Enzyme-mediated relief of proteotoxic stress and protein aggregation in vivo can also occur without degradation but is not dependent on robust ATP hydrolysis. Degron binding regulates the activities of the AAA+ Lon protease in addition to targeting proteins for degradation, degron binding regulates Lon ATPase and protease activity in addition to serving a recognition function. Inactivation of cell-division inhibitor SulA in vivo requires binding to the N domain and robust ATP hydrolysis but does not require degradation or translocation into the proteolytic chamber
physiological function
-
Lon-DNA interactions are essential for Lon activity in cell division control. The ability of Lon to bind DNA is determined by its ATPase domain. This binding is required for processing protein substrates in nucleoprotein complexes, and Lon may help regulate DNA replication in response to growth conditions
additional information
the C-terminal part of the HI(CC) domain has an allosteric effect on the efficiency of the functioning of both ATPase and proteolytic sites of the enzyme, while the coiled-coil (CC) fragment of this domain interacts with the protein substrate. Analysis of the propensity of C-His-Lon and mutant enzymes Lon-R164A, Lon-R192A, and Lon-Y294A for utodegradation reveals that Lon-Y294A is most prone to autolysis. Slight autolysis of the intact enzyme and the mutant forms of Lon-R164A and Lon-R192A is observed only in the absence of nucleotides
additional information
-
the C-terminal part of the HI(CC) domain has an allosteric effect on the efficiency of the functioning of both ATPase and proteolytic sites of the enzyme, while the coiled-coil (CC) fragment of this domain interacts with the protein substrate. Analysis of the propensity of C-His-Lon and mutant enzymes Lon-R164A, Lon-R192A, and Lon-Y294A for utodegradation reveals that Lon-Y294A is most prone to autolysis. Slight autolysis of the intact enzyme and the mutant forms of Lon-R164A and Lon-R192A is observed only in the absence of nucleotides
additional information
the CC region is involved in the recognition of the nucleotide nature by the enzyme and the interaction of the enzyme with the protein substrate, effect of the coiled-coil (CC) region of the alpha-helical inserted domain of Escherichia coli Lon protease (Ec-Lon) on the functional activity of the enzyme, overview. The CC region is necessary for the formation and functioning of the ATPase and peptidase active centers, the occurrence of allosteric interactions between them, and for the implementation of proteolysis by a unique processive mechanism
additional information
the enzyme Ec-Lon is a bifunctional homohexameric enzyme, its subunit comprises an N-terminal noncatalytic region, two-domain ATPase module, and a proteolytic domain with serine-lysine endopeptidase activity
additional information
the enzyme's active site has a Ser-Lys catalytic dyad
additional information
-
the AAA+ ATPase module and protease domain of Lon are part of a single polypeptide
additional information
-
the second alpha-helical domain plays a crucial role in ATP hydrolysis and enzyme binding to the target protein, while the first alpha-helical domain is not important for the manifestation of the catalytic properties of the enzyme, but it affects the functioning of Lon ATPase and peptidase sites and is involved in maintaining enzyme stability, participation of the first alpha-helical domain in the formation of three-dimensional structures of LonA proteases and/or their complexes with DNA
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
525000
-
hexamer, gel filtration and sedimentation velocity analytical ultracentrifugation
840000 - 900000
-
E. coli, calculated from sedimentation coefficient and Stokes radius
87000
930000
-
dodecamer, gel filtration and sedimentation velocity analytical ultracentrifugation
94000
additional information
additional information
-
E. coli enzyme behaves as apparent tetramer or octamer on gel filtration
additional information
-
amino acid sequence compared to other Lon-protein sequences
additional information
-
amino acid sequence compared to other Lon-protein sequences
additional information
-
amino acid sequence compared to other Lon-protein sequences
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dodecamer
the larger assembly has decreased ATPase activity and displays substrate-specific alterations in degradation compared to the hexamer. The enzyme dodecamer successfully completes many of the Lon protease's important regulatory functions while modifying substrate choice, perhaps to better manage protein quality control under conditions such as UV, heat, and oxidative stress. Identification of N domain interactions underlying Lon dodecamer formation. The Lon N domains are primarily responsible for dodecamer formation, the Lon dodecamer forms via putative N domain coiled-coil interactions. Analytical ultracentrifugation
homohexamer
dodecamer
-
hexamers of Escherichia coli Lon also interact to form a dodecamer at physiological protein concentrations, the dodecamer shows a prolate structure with the protease chambers at the distal ends and a matrix of N domains forming an equatorial hexamer-hexamer interface, with portals of about 45 A providing access to the enzyme lumen
hexamer
homooligomer
-
the subunits are formed by five successively connected domains, i.e., N-terminal domain, alpha-helical domain, nucleotide-binding domain, second alpha-helical domain, and proteolytic domain, domain organization, overview
multimer
oligomer
tetramer
additional information
homohexamer
Lon assembles into a barrel-shaped homohexamer with the proteolytic active sites sequestered in an internal chamber, largely inaccessible to folded proteins. This architecture serves to prevent degradation of non-substrate proteins. Analysis of hexamer-hexamer interactions, usage of an ellipsoidal electron density map sufficient to model two barrel-shaped hexamers at the distal ends of the dodecamer corresponding to the Lon ATPase and protease modules. The two barrels are bridged by six extended helical structures, which are modeled as six N domain dimers forming end-to-end interactions that mimic two-stranded, antiparallel coiled coils
hexamer
-
negative stain electron microscopy, crystallography of the proteolytic domain
additional information
each Lon monomer contains three functional subregions: the N domain, AAA+ ATPase module, and a protease domain. The ATPase and protease domains are the most well-conserved regions of Lon
additional information
-
each Lon monomer contains three functional subregions: the N domain, AAA+ ATPase module, and a protease domain. The ATPase and protease domains are the most well-conserved regions of Lon
additional information
enzyme Ec-Lon subunit includes an ATPase component and a proteolytic component (AAA+ module and P-domain, respectively), as well as a noncatalytic region formed by the N-terminal (N) domain and an inserted alpha-helical (HI(CC)) domain. This region is unique for AAA+ proteins. The C-terminal part of the HI(CC) domain has an allosteric effect on the efficiency of the functioning of both ATPase and proteolytic sites of the enzyme, while the coiled-coil (CC) fragment of this domain interacts with the protein substrate. The HI(CC) domain is not essential for the formation of the ATPase center of Ec-Lon protease, but still has an effect on the functional efficiency of this center. Detailed analysis and comparisons of primary and secondary structures of the HI(CC) domain in AAA* proteases, overview
additional information
-
enzyme Ec-Lon subunit includes an ATPase component and a proteolytic component (AAA+ module and P-domain, respectively), as well as a noncatalytic region formed by the N-terminal (N) domain and an inserted alpha-helical (HI(CC)) domain. This region is unique for AAA+ proteins. The C-terminal part of the HI(CC) domain has an allosteric effect on the efficiency of the functioning of both ATPase and proteolytic sites of the enzyme, while the coiled-coil (CC) fragment of this domain interacts with the protein substrate. The HI(CC) domain is not essential for the formation of the ATPase center of Ec-Lon protease, but still has an effect on the functional efficiency of this center. Detailed analysis and comparisons of primary and secondary structures of the HI(CC) domain in AAA* proteases, overview
additional information
the Ec-Lon subunit comprises N-terminal non-catalytic region, ATPase module and proteolytic domain (serine-lysine endopeptidase)
additional information
the inserted alpha-helical HI(CC) domain is necessary for the formation of the ATPase center of the Ec-Lon protease and its correct functioning
additional information
-
the inserted alpha-helical HI(CC) domain is necessary for the formation of the ATPase center of the Ec-Lon protease and its correct functioning
additional information
-
electron-microscope analysis, enzyme has a six-membered, ring-shaped structure with a central cavity. Side-on view shows a two-layered structure
additional information
-
isolated proteolytic domain LonP, obtained by limited proteolysis, exhibits both peptidase and proteolytic activity, but cleaves large protein substrates at a significantly lower rate than the full size protease. LonAP fragment, containing both the ATPase and the proteolytic domains, retains almost all of the enzymawtic properties of the full-size protein. both LonP and LonAP predominantly form dimers unlike the native protease Lon functioning as a tetramer
additional information
-
the ATPase fragment isolated after chymotryptic digestion of the protein has no ATPase activity in spite of its ability to bind nucleotides. It is monomeric in solution. The isolated monomeric proteolytic fragment does not display proteolytic activity. The intact ATPase/proteolytic fragment forms dimers and tetramers and exhibits properties of a non-processive protease and show ATPase activity with self-degradation upon ATP hydrolysis
additional information
-
compared with hexamers, enzyme dodecamers are much less active in degrading large substrates but equally active in degrading small substrates
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
N-terminal residues 1-245 comprising most of the N-terminal domain of the enzyme, as selenomethionine derivative to 2.6 A resolution. The molecule consists of two compact subdomains and a very long C-terminal alpha-helix. The structure of the first subdomain, residues 1-117, which consists mostly of beta-strands, is similar to that of the shorter fragment, whereas the second subdomain is almost entirely helical. The fold and spatial relationship of the two subdomains, with the exception of the C-terminal helix, closely resemble the structure of BPP1347, a 203-amino-acid protein of unknown function from Bordetella parapertussis
digestion of lonA by alpha-chymotrypsin yields a stable fragment consisting of residues 491-584 crystallized. Crystal structure of the proteolytic domain of lonA (residues 585-784) elucidates a unique fold, P31 space group
-
inactive Lon-S679A P-domain successfully crystallized by the hanging drop vapor diffusion method
-
investigation of the mode of peptide interaction with the proteolytically inactive Lon mutant S679A in the absence and presence of ADP or AMPPNP shows that the binding interaction between protein and peptide varies with the nucleotide bound to the enzyme
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q220C
site-directed mutagenesis, the mutant reproducibly yields fast and robust intermolecular disulfide crosslinking. The cysteine-based disulfide crosslinking is responsible for the formation of the SDS-resistant dimers
R164A
site-directed mutagenesis, mutation of a HI(CC) domain residue, helix H3, the mutant shows highly reduced ATPase activity in presence of beta-casein compared to the wild-type
R192A
site-directed mutagenesis, mutation of a HI(CC) domain residue, the mutant shows highly reduced ATPase activity in presence of beta-casein compared to the wild-type
S679A
V217A/Q220A
site-directed mutagenesis, residues Val217 and Gln220 are present in a region predicted to form intermolecular coiled coils between hexamers, the Lon mutant variant (LonVQ) forms a dodecamer with increased stability compared to wild-type. The dodecamer is active, but it exhibits alterations in substrate selection and/or degradation. Mutant LonVQ is altered in recognition of dodecamer-sensitive substrates in vivo
V217C
site-directed mutagenesis, the mutant reproducibly yields fast and robust intermolecular disulfide crosslinking. The cysteine-based disulfide crosslinking is responsible for the formation of the SDS-resistant dimers
Y294A
site-directed mutagenesis, mutation of a HI(CC) domain residue, the mutant shows highly reduced ATPase activity in presence of beta-casein compared to the wild-type
D676N
E424Q
-
site-directed mutagenesis, the mutant is unable to inactivate SulA in vivo and displays reduced rates of both basal and substrate-stimulated ATP hydrolysis. The mutant translocates and degrades CM-titinI27-sul20 and CM-titinI27-beta20 at a very slow rate. The mutation stabilizes the enzyme conformation that is active in relieving stress
E424Q/S679A
-
site-directed mutagenesis, the mutant is unable to inactivate SulA in vivo and displays reduced rates of both basal and substrate-stimulated ATP hydrolysis
E614K
K362Q
-
intersubunit domain-domain interactions between ATPase and proteolytic sites by complementation
K371E/K376E/R379E
-
site-directed mutagenesis, mutant demonstrates significantly reduced DNA binding capabilities compared to wild-type enzyme. The Lon mutant does not restore cell length in the lon-/- strain, cells remained filamentous
R164A
-
site-directed mutagenesis, the ATPase activity of the mutant is markedly reduced compared to the wild-type enzyme, thhe mutant retains the ability to hydrolyze PepTBE in the absence of effectors
R306E/K308E/K310E/K311E
-
site-directed mutagenesis, the mutant demonstrates significantly reduced DNA binding capabilities compared to wild-type enzyme. The Lon mutant does not restore cell length in the lon-/- strain, cells remained filamentous
R542A
-
site-directed mutagenesis, the mutant completely loses its ability to hydrolyze ATP, the mutant retains the ability to hydrolyze PepTBE in the absence of effectors
S679A
S679W
Y398A
-
site-directed mutagenesis, the mutant has basal ATP-hydrolysis activity similar to wild-type Lon, but displays substantially reduced rates of ATP hydrolysis in the presence of sul20- or beta20-tagged substrates
additional information
S679A
site-directed mutagenesis, the Lon trapping variant is able to translocate substrates but unable to degrade them, it is established and used for substrate determinations by mass spectrometry
D676N
-
is completely inactive for protein degradation, it retains some basal ATPase activity, but no activation of ATPase activity occurs upon binding of protein substrates
E614K
-
is a dominant-negative mutant, can form mixed oligomers with wild-type lon and interferes with its activity
E614K
-
mixed oligomeric complexes composed of wild-type lon and the inactive lon E614K mutant, results in an enzymatically inactive protein
S679A
-
inactive, intersubunit domain-domain interactions between ATPase and proteolytic sites by complementation
S679A
-
proteolytically inactive, but wild-type-like intrinsic and peptide-stimulated ATPase activitiy. Two-step peptide S4 binding event, where a conformational change occurs after a rapid equilibrium peptide binding step
S679A
-
complete loss of activity. Mutant is not capable of restoring the secB cold sensitive phenotype, indicating that the deleterious effect of Lon in the secB mutant is due to its protease activity
S679A
-
site-directed mutagenesis, the S679A mutation destabilizes the enzyme conformation that is active in relieving stress
S679W
-
proteolytically inactive mutant. ATPase activity is affected by a variety of mutations generated at the vicinity of the proteolytic site Ser 679. Mutation of the ATP-binding site abolishes both the ATPase and protease activities of lon
S679W
-
proteolytically inactive, but wild-type-like intrinsic and peptide-stimulated ATPase activitiy. Two-step peptide S4 binding event, where a conformational change occurs after a rapid equilibrium peptide binding step
additional information
analysis of the propensity of C-His-Lon and mutant enzymes Lon-R164A, Lon-R192A, and Lon-Y294A for autodegradation reveals that Lon-Y294A is most prone to autolysis. Slight autolysis of the intact enzyme and the mutant forms of Lon-R164A and Lon-R192A is observed only in the absence of nucleotides
additional information
-
analysis of the propensity of C-His-Lon and mutant enzymes Lon-R164A, Lon-R192A, and Lon-Y294A for autodegradation reveals that Lon-Y294A is most prone to autolysis. Slight autolysis of the intact enzyme and the mutant forms of Lon-R164A and Lon-R192A is observed only in the absence of nucleotides
additional information
construction of a recombinant form des-CC(G5)-Lon in which the deleted CC fragment, a deleted 108-unit coiled-coil fragment (residues M173-M280) is replaced by a pentaglycine peptide, the the ClpB chaperone of Thermus thermophilus. Analysis of enzymatic properties of des-CC(G5)-Lon-H6 (DELTArLon) mutant, overview. In the absence of nucleotide effectors as well as in the presence of free nucleotides or the ADP-Mg complex, casein is not hydrolyzed by rLon even if the duration of the experiment is increased many times. The deletion form DELTArLon is incapable of hydrolyzing beta-casein in the time interval in which the proteolytic activity of full-length rLon protease is tested
additional information
construction of an N-terminally truncated ClpX lacking residues 1-62, ClpXDELTAN
additional information
removal of the HI(CC) domain, deletion of the HI(CC) domain leads to a complete loss of the proteolytic activity towards beta-casein by the deletion form. The deletion form Lon-dHI(CC) is unstable and it undergoes autolysis both in the absence and presence of nucleotide effectors, the autolysis of Lon-dHI(CC) is most pronounced in the presence of Mg2+ ions
additional information
-
removal of the HI(CC) domain, deletion of the HI(CC) domain leads to a complete loss of the proteolytic activity towards beta-casein by the deletion form. The deletion form Lon-dHI(CC) is unstable and it undergoes autolysis both in the absence and presence of nucleotide effectors, the autolysis of Lon-dHI(CC) is most pronounced in the presence of Mg2+ ions
additional information
-
overproduction of enzyme is lethal. Overproduction specifically inhibits translation through specific activation of YoeB-dependent mRNA cleavage
additional information
-
in an endogenous protein tagging assay, lon mutants accumulate excessive levels of tmRNA-tagged proteins. In a reporter protein tagging assay with lambda-CI-N, lon mutants efficiently tag the reporter protein, but the tagged protein exhibits increased stability. GFP construct containing a hard-coded C-terminal tmRNA tag exhibits increased stability in lon mutant cells
additional information
-
lon clp ppk triple mutant, rate of protein turnover ist nearly identical to that of the lon clp double mutant. Deletion mutants of lon fused to the C-terminus of maltose-binding protein
additional information
-
lon gene mutants, form long undivided filaments upon UV irradiation
additional information
-
lon mutant altered in substrate specificity. A mutation in lon that converts Glu240 to Lys results in stabilization of lon substrate RcsA in vivo but does not affect the degradation of lon substrate SulA. lon lacking 107 N-terminal residues has drastically reduced protein degrading activity in vitro
additional information
-
lon mutant, confers partial resistance against colicin. Sensitivity of lon mutant to colicin can be rescued by complementation. Decrease in the protein expression levels of BtuB and OmpF in the lon mutant, which are involved in colicin translocation. Elevation of expression of the oxyS gene, which can negatively control on the expression of BtuB protein
additional information
-
lon mutants, accumulate abnormal proteins, form mucoid colonies and long filaments, fail to adapt rapidly to a nutrional downshift, are sensitive to UV at 30°C because of SulA accumulation, at higher temperatures they lose their sensitivity because ClpYQ takes over SulA degredation
additional information
-
lon- mutants survive equally well under aerobic conditions as the wild-type, but die more rapidly than the wild-type under anaerobiosis. Effect is not mediated through a compensatory increase in the Clp protease
additional information
-
in gene disruption mutant lon::Tn10 members of the RcsA regulon and many genes of the sigmaS-dependent general stress response are upregulated. The lon mutation does not affect sigmaS levels nor sigmaS activity in general. Lon-affected genes also include the major acid resistance genes
additional information
-
the combined absence of Lon and SecB leads to a significant increase in protein aggregation at 37°C. The most abundant aggregated species are proteins destined for export. Data suggest that Lon and SecB share some substrates and that the SecB chaperone protects them from Lon degradation at both high and low temperatures
additional information
-
construction of enzyme mutants, fusion of the Lon N domain to Escherichia coli ClpXDELTAN, a AAA+ enzyme that forms stable ring hexamers. Chimera307 contained the entire Lon N domain (residues 1-307) fused to ClpXDELTAN, whereas chimera211 contains the first 211 residues of Lon, which includes a globular region of the N domain but not an extended helical region. In addition, chimera211 contains disulfide bonds between the subunits of ClpXDELTAN, which have been shown to stabilize functional covalent hexamers. The ClpXDELTAN hexamerization is required for functional interaction with ClpP
additional information
-
generation of mutant LonDELTANP lacking the ATP domain. Deletion of Lon's ATPase domain abrogates interactions with DNA. The DNA-binding defect of Lon protease affects TrfA proteolysis. And the Lon mutants are defective in proper cellular localization, most probably due to their impaired ability to form a nucleoprotein complex
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21
-
rapid loss of activity in the absence of glycerol. ATP, AMP-PNP or ADP stabilizes, E. coli
30 - 37
-
can substitute for yeast protease at 30°C, but inable to maintain respiration at 37°C
42
-
1 h, 80% loss of activity, 3 mM ATP stabilizes, ADP or AMP less effectively, not Mg2+
additional information
-
loses DNA-binding ability, not ATP-dependent protease activity after heat-shock treatment
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ELon ist quite stable against digestion by trypsin, ADP binding does not protect. ELon binds to ADP and undergoes at least one structural change that exposes a tryptic digestion site
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, in 20-30 glycerol, many months, with prolonged storage the enzyme exhibits ATP-independent peptidase activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged enzyme mutant from Escherichia coli by nickel affinity chromatography and gel filtration
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain CH1019 by nickel affinity chromatography
recombinant N-terminally truncated ClpX lacking residues 1-62, from Escherichia coli strain BL21(DE3)
recombinant wild-type and mutant enzymes from Escherichia coli strain W3110
by successive Ni2+-NTA affinity chromatography and anion-exchange chromatography
-
lon-N119 purified. Digestion of lonA by alpha-chymotrypsin yields a stable fragment consisting of residues 491-584 purified. lon proteolytic domain purified
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene lon, functional recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain CH1019
gene lon, functional recombinant expression of wild-type and mutant enzymes in Escherichia coli strain W3110
gene lon, recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
gene lon, recombinant expression of His-tagged enzyme mutant in Escherichia coli
gene lon, recombinant expression of N-terminally truncated ClpX lacking residues 1-62, i.e. ClpXDELTAN, in Escherichia coli strain BL21(DE3)
C-terminally His6-tagged lon expressed in Escherichia coli strain CH1019 carrying lon expression plasmid pET21b-LonH6
-
cloned and expressed in Saccharomyces cerevisiae, Lon protease substitutes for PIM1 protease
-
cloning of the P-domain, expression as MBP fusion protein in Escherichia coli BL21 (DE3)
-
PCR fragment cloned into expression vector pQE30 and transformed into the lon-deficient mutant
-
wild-type and mutant enzymes cloned and expressed in Escherichia coli BL21
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
-
protein synthesis in Escherichia coli, enzyme and protease Clp participate in the physiological disintegration of cytoplasmic inclusion bodies, their absence minimizing the protein removal up to 40%. Clp takes the major and enzyme a minor role in processing of aggregation-prone proteins and also of polypeptides physiologically released from inclusion bodies
additional information
additional information
-
lon causes proteolysis of normal proteins in cells and is lethal to host cells. lon-polyphosphate complex is the missing link between protein degradation and the phenomen of stringent response. The complex between lon and polyphosphate is formed during the stringent response, whereon degrades at lest free ribosomal proteins, providing amino acids for synthesizing enzymes required for adaption to a nutrient-poor environment
additional information
-
lon plays a role in protein quality control by destroying unfolded proteins, it participates in regulatory circuits by controlling amount and availability of specific substrates
additional information
-
plays vital roles in maintaining cellular functions by selectively eliminating misfolded, damaged and certain short-lived regulatory proteins. lon is essential for cellular homeostasis, mediating protein quality control and metabolic regulation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Waxman, L.; Goldberg, A.L.
Protease La from Escherichia coli hydrolyzes ATP and proteins in a linked fashion
Proc. Natl. Acad. Sci. USA
79
4883-4887
1982
Escherichia coli
Larimore, F.S.; Waxman, L.; Goldberg, A.L.
Studies of the ATP-dependent proteolytic enzyme, protease La, from Escherichia coli
J. Biol. Chem.
257
4187-4195
1982
Escherichia coli
Waxman, L.; Goldberg, A.L.
Protease La, the lon gene product, cleaves specific fluorogenic peptides in an ATP-dependent reaction
J. Biol. Chem.
260
12022-12028
1985
Escherichia coli
Goldberg, A.L.; Waxman, L.
The role of ATP hydrolysis in the breakdown of proteins and peptides by protease La from Escherichia coli
J. Biol. Chem.
260
12029-12034
1985
Escherichia coli
Waxman, L.; Goldberg, A.L.
Selectivity of intracellular proteolysis: protein substrates activate the ATP-dependent protease (La)
Science
232
500-503
1986
Escherichia coli
Sonezaki, S.; Okita, K.; Oba, T.; Ishii, Y.; Kondo, A.; Kato, Y.
Protein substrates and heat shock reduce the DNA-binding ability of Escherichia coli Lon protease
Appl. Microbiol. Biotechnol.
44
484-488
1995
Escherichia coli
Edmunds, T.; Goldberg, A.L.
Role of ATP hydrolysis in the degradation of proteins by protease La from Escherichia coli
J. Cell. Biochem.
32
187-191
1986
Escherichia coli
Goldberg, A.L.; Menon, A.S.; Goff, S.; Chin, D.T.
The mechanism and regulation of the ATP-dependent protease La from Escherichia coli
Biochem. Soc. Trans.
15
809-811
1987
Escherichia coli
Maurizi, M.R.
Degradation in vitro of bacteriophage lambda N protein by Lon protease from Escherichia coli
J. Biol. Chem.
262
2696-2703
1987
Escherichia coli
Menon, A.S.; Waxman, L.; Goldberg, A.L.
The energy utilized in protein breakdown by the ATP-dependent protease (La) from Escherichia coli
J. Biol. Chem.
262
722-726
1987
Escherichia coli
Menon, A.S.; Goldberg, A.L.
Binding of nucleotides to the ATP-dependent protease La from Escherichia coli
J. Biol. Chem.
262
14921-14928
1987
Escherichia coli
Menon, A.S.; Goldberg, A.L.
Protein substrates activate the ATP-dependent protease La by promoting nucleotide binding and release of bound ADP
J. Biol. Chem.
262
14929-14934
1987
Escherichia coli
Chin, D.T.; Goff, S.; Webster, T.; Smith, T.; Goldberg, A.L.
Sequence of the lon gene in Escherichia coli. A heat-shock gene which encodes the ATP-dependent protease La
J. Biol. Chem.
263
11718-11728
1988
Escherichia coli
Baker, M.E.
Location of enzymatic and DNA-binding domains on E. coli protease La
FEBS Lett.
244
31-33
1989
Escherichia coli
Modha, J.; Weiner, D.P.; Cullis, P.M.; Rivett, A.J.
Effects of ATP analogues on the activity of the ion proteinase of Escherichia coli
Biochem. Soc. Trans.
18
589
1990
Escherichia coli
Suzuki, C.K.; Kutejova, E.; Suda, K.
Analysis and purification of ATP-dependent mitochondrial lon protease of Saccharomyces cerevisiae
Methods Enzymol.
260
486-494
1995
Saccharomyces cerevisiae, Escherichia coli
Wang, N.; Gottesman, S.; Willingham, M.C.; Gottesman, M.M.; Maurizi, M.R.
A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease
Proc. Natl. Acad. Sci. USA
90
11247-11251
1993
Brevibacillus brevis, Escherichia coli, Homo sapiens, Homo sapiens (P36776), Myxococcus xanthus
Fischer, H.; Glockshuber, R.
ATP hydrolysis is not stoichiometrically linked with proteolysis in the ATP-dependent protease La from Escherichia coli
J. Biol. Chem.
268
22502-22507
1993
Escherichia coli
Sonezaki, S.; Konda, A.; Oba, T.; Ishii, Y.; Kato, Y.; Nakayama, H.
Overproduction and purification of Lon protease from Escherichia coli using a maltose-binding protein fusion system
Appl. Microbiol. Biotechnol.
42
313-318
1994
Escherichia coli
Goldberg, A.L.; Moerschell, R.P.; Chung, C.H.; Maurizi, M.R.
ATP-dependent protease La (lon) from Escherichia coli
Methods Enzymol.
244
350-375
1994
Brevibacillus brevis, Saccharomyces cerevisiae, Escherichia coli, Myxococcus xanthus, Rattus norvegicus
Goldberg, A.L.
The mechanism and functions of ATP-dependent proteases in bacterial and animal cells
Eur. J. Biochem.
203
9-23
1992
Bos taurus, Escherichia coli, Rattus norvegicus
Chung, C.H.; Goldberg, A.L.
The product of the lon (capR) gene in Escherichia coli is the ATP-dependent protease, protease La
Proc. Natl. Acad. Sci. USA
78
4931-4935
1981
Escherichia coli
Oh, J.Y.; Eun, Y.M.; Yoo, S.J.; Seol, J.H.; Seong, I.S.; Lee, C.S.; Chung, C.H.
LonR9 carrying a single Glu614 to Lys mutation inhibits the ATP-dependent protease La (Lon) by forming mixed oligomeric complexes
Biochem. Biophys. Res. Commun.
250
32-35
1998
Escherichia coli, Escherichia coli RGC123
Roudiak, S.G.; Seth, A.; Knipfer, N.; Shrader, T.E.
The lon protease from Mycobacterium smegmatis: molecular cloning, sequence analysis, functional expression, and enzymatic characterization
Biochemistry
37
377-386
1998
Escherichia coli, Mycolicibacterium smegmatis
Thomas-Wohlever, J.; Lee, I.
Kinetic characterization of the peptidase activity of Escherichia coli lon reveals the mechanistic similarities in ATP-dependent hydrolysis of peptide and protein substrates
Biochemistry
41
9418-9425
2002
Escherichia coli
Nishii, W.; Maruyama, T.; Matsuoka, R.; Muramatsu, T.; Takahashi, K.
The unique sites in SulA protein preferentially cleaved by ATP-dependent Lon protease from Escherichia coli
Eur. J. Biochem.
269
451-457
2002
Escherichia coli
Starkova, N.N.; Koroleva, E.P.; Rumsh, L.D.; Ginodman, L.M.; Rotanova, T.V.
Mutations in the proteolytic domain of Escherichia coli protease Lon impair the ATPase activity of the enzyme
FEBS Lett.
422
218-220
1998
Escherichia coli
Rasulova, F.S.; Dergousova, N.I.; Starkova, N.N.; Melnikov, E.E.; Rumsh, L.D.; Ginodman, L.M.; Rotanova, T.V.
The isolated proteolytic domain of Escherichia coli ATP-dependent protease Lon exhibits the peptidase activity
FEBS Lett.
432
179-181
1998
Escherichia coli, Escherichia coli MH-1
Vasilyeva, O.V.; Kolygo, K.B.; Leonova, Y.F.; Potapenko, N.A.; Ovchinnikova, T.V.
Domain structure and ATP-induced conformational changes in Escherichia coli protease Lon revealed by limited proteolysis and autolysis
FEBS Lett.
526
66-70
2002
Escherichia coli
van Dyck, L.; Neupert, W.; Langer, T.
The ATP-dependent PIM1 protease is required for the expression of intron-containing genes in mitochondria
Genes Dev.
12
1515-1524
1998
Saccharomyces cerevisiae, Escherichia coli
Ebel, W.; Skinner, M.M.; Dierksen, K.P.; Scott, J.M.; Trempy, J.E.
A conserved domain in Escherichia coli Lon protease is involved in substrate discriminator activity
J. Bacteriol.
181
2236-2243
1999
Escherichia coli
Botos, I.; Melnikov, E.E.; Cherry, S.; Tropea, J.E.; Khalatova, A.G.; Rasulova, F.; Dauter, Z.; Maurizi, M.R.; Rotanova, T.V.; Wlodawer, A.; Gustchina, A.
The catalytic domain of E.coli Lon protease has a unique fold and a Ser-Lys dyad in the active site
J. Biol. Chem.
279
8140-8148
2003
Escherichia coli, Homo sapiens
Teichmann, U.; van Dyck, L.; Guiard, B.; Fischer, H.; Glockshuber, R.; Neupert, W.; Langer, T.
Substitution of PIM1 protease in mitochondria by Escherichia coli Lon protease
J. Biol. Chem.
271
10137-10142
1996
Saccharomyces cerevisiae, Escherichia coli
Fu, G.K.; Smith, M.J.; Markovitz, D.M.
Bacterial protease Lon is a site-specific DNA-binding protein
J. Biol. Chem.
272
534-538
1997
Escherichia coli, Escherichia coli Y1089
Hilliard, J.J.; Simon, L.D.; Van Melderen, L.; Maurizi, M.R.
PinA inhibits ATP hydrolysis and energy-dependent protein degradation by Lon protease
J. Biol. Chem.
273
524-527
1998
Escherichia coli
Smith, C.K.; Baker, T.A.; Sauer, R.T.
Lon and Clp family proteases and chaperones share homologous substrate-recognition domains
Proc. Natl. Acad. Sci. USA
96
6678-6682
1999
Escherichia coli
Patterson, J.; Vineyard, D.; Thomas-Wohlever, J.; Behshad, R.; Burke, M.; Lee, I.
Correlation of an adenine-specific conformational change with the ATP-dependent peptidase activity of Escherichia coli Lon
Biochemistry
43
7432-7442
2004
Escherichia coli
Vineyard, D.; Patterson-Ward, J.; Berdis, A.J.; Lee, I.
Monitoring the timing of ATP hydrolysis with activation of peptide cleavage in Escherichia coli Lon by transient kinetics
Biochemistry
44
1671-1682
2005
Escherichia coli
Rotanova, T.V.; Melnikov, E.E.; Khalatova, A.G.; Makhovskaya, O.V.; Botos, I.; Wlodawer, A.; Gustchina, A.
Classification of ATP-dependent proteases Lon and comparison of the active sites of their proteolytic domains
Eur. J. Biochem.
271
4865-4871
2004
Escherichia coli
Nishii, W.; Suzuki, T.; Nakada, M.; Kim, Y.T.; Muramatsu, T.; Takahashi, K.
Cleavage mechanism of ATP-dependent Lon protease toward ribosomal S2 protein
FEBS Lett.
579
6846-6850
2005
Escherichia coli
Nomura, K.; Kato, J.; Takiguchi, N.; Ohtake, H.; Kuroda, A.
Effects of inorganic polyphosphate on the proteolytic and DNA-binding activities of Lon in Escherichia coli
J. Biol. Chem.
279
34406-34410
2004
Escherichia coli
Vera, A.; Aris, A.; Carrio, M.; Gonzalez-Montalban, N.; Villaverde, A.
Lon and ClpP proteases participate in the physiological disintegration of bacterial inclusion bodies
J. Biotechnol.
119
163-171
2005
Escherichia coli
Botos, I.; Melnikov, E.E.; Cherry, S.; Khalatova, A.G.; Rasulova, F.S.; Tropea, J.E.; Maurizi, M.R.; Rotanova, T.V.; Gustchina, A.; Wlodawer, A.
Crystal structure of the AAA+ alpha domain of E. coli Lon protease at 1.9A resolution
J. Struct. Biol.
146
113-122
2004
Escherichia coli
Park, S.C.; Jia, B.; Yang, J.K.; Van, D.L.; Shao, Y.G.; Han, S.W.; Jeon, Y.J.; Chung, C.H.; Cheong, G.W.
Oligomeric structure of the ATP-dependent protease La (Lon) of Escherichia coli
Mol. Cell
21
129-134
2006
Escherichia coli
Christensen, S.K.; Maenhaut-Michel, G.; Mine, N.; Gottesman, S.; Gerdes, K.; Van Melderen, L.
Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system
Mol. Microbiol.
51
1705-1717
2004
Escherichia coli
Li, M.; Rasulova, F.; Melnikov, E.E.; Rotanova, T.V.; Gustchina, A.; Maurizi, M.R.; Wlodawer, A.
Crystal structure of the N-terminal domain of E. coli Lon protease
Protein Sci.
14
2895-2900
2005
Escherichia coli
Vasilyeva, O.V.; Martynova, N.Y.; Potapenko, N.A.; Ovchinnikova, T.V.
Isolation and characterization of fragments of the ATP-dependent protease Lon from Escherichia coli obtained by limited proteolysis
Russ. J. Bioorg. Chem.
30
306-314
2004
Escherichia coli
-
Luo, S.; McNeill, M.; Myers, T.G.; Hohman, R.J.; Levine, R.L.
Lon protease promotes survival of Escherichia coli during anaerobic glucose starvation
Arch. Microbiol.
189
181-185
2008
Escherichia coli
Lee, Y.Y.; Hu, H.T.; Liang, P.H.; Chak, K.F.
An E. coli lon mutant conferring partial resistance to colicin may reveal a novel role in regulating proteins involved in the translocation of colicin
Biochem. Biophys. Res. Commun.
345
1579-1585
2006
Escherichia coli, Escherichia coli K12 MG1655
Vineyard, D.; Zhang, X.; Lee, I.
Transient kinetic experiments demonstrate the existence of a unique catalytic enzyme form in the peptide-stimulated ATPase mechanism of Escherichia coli Lon protease
Biochemistry
45
11432-11443
2006
Escherichia coli
Vineyard, D.; Patterson-Ward, J.; Lee, I.
Single-turnover kinetic experiments confirm the existence of high- and low-affinity ATPase sites in Escherichia coli Lon protease
Biochemistry
45
4602-4610
2006
Escherichia coli
Patterson-Ward, J.; Huang, J.; Lee, I.
Detection and characterization of two ATP-dependent conformational changes in proteolytically inactive Escherichia coli Lon mutants by stopped flow kinetic techniques
Biochemistry
46
13593-13605
2007
Escherichia coli
Lee, I.; Suzuki, C.K.
Functional mechanics of the ATP-dependent Lon protease- lessons from endogenous protein and synthetic peptide substrates
Biochim. Biophys. Acta
1784
727-735
2008
Saccharomyces cerevisiae, Brucella abortus, Caulobacter vibrioides, Escherichia coli, Homo sapiens, Mycolicibacterium smegmatis, Pseudomonas aeruginosa, Rattus norvegicus, Salmonella enterica subsp. enterica serovar Typhimurium, Thermoplasma acidophilum
Kuroda, A.
A polyphosphate-lon protease complex in the adaptation of Escherichia coli to amino acid starvation
Biosci. Biotechnol. Biochem.
70
325-331
2006
Escherichia coli
Choy, J.S.; Aung, L.L.; Karzai, A.W.
Lon protease degrades transfer-messenger RNA-tagged proteins
J. Bacteriol.
189
6564-6571
2007
Escherichia coli
Lee, I.; Berdis, A.J.; Suzuki, C.K.
Recent developments in the mechanistic enzymology of the ATP-dependent Lon protease from Escherichia coli: highlights from kinetic studies
Mol. Biosyst.
2
477-483
2006
Saccharomyces cerevisiae, Brucella abortus, Escherichia coli, Homo sapiens, Salmonella enterica subsp. enterica serovar Typhimurium
Rotanova, T.V.; Botos, I.; Melnikov, E.E.; Rasulova, F.; Gustchina, A.; Maurizi, M.R.; Wlodawer, A.
Slicing a protease: structural features of the ATP-dependent Lon proteases gleaned from investigations of isolated domains
Protein Sci.
15
1815-1828
2006
Archaeoglobus fulgidus, Bordetella parapertussis, Saccharomyces cerevisiae, Escherichia coli, Methanocaldococcus jannaschii, Mycolicibacterium smegmatis, Brevibacillus thermoruber
Tsilibaris, V.; Maenhaut-Michel, G.; Van Melderen, L.
Biological roles of the Lon ATP-dependent protease
Res. Microbiol.
157
701-713
2006
Brevibacillus brevis, Bacillus subtilis, Saccharomyces cerevisiae, Caulobacter vibrioides, Escherichia coli, Homo sapiens, Myxococcus xanthus, no activity in Lactobacillus sp., no activity in Streptococcus sp., Yersinia pestis, Proteus mirabilis, Pseudomonas syringae, Salmonella enterica subsp. enterica serovar Typhimurium, Streptomyces lividans, Vibrio parahaemolyticus, no activity in Mycobacterium tuberculosis, no activity in Mycobacterium leprae
Melnikov, E.E.; Andrianova, A.G.; Morozkin, A.D.; Stepnov, A.A.; Makhovskaya, O.V.; Botos, I.; Gustchina, A.; Wlodawer, A.; Rotanova, T.V.
Limited proteolysis of E. coli ATP-dependent protease Lon - a unified view of the subunit architecture and characterization of isolated enzyme fragments
Acta Biochim. Pol.
55
281-296
2008
Escherichia coli
Patterson-Ward, J.; Tedesco, J.; Hudak, J.; Fishovitz, J.; Becker, J.; Frase, H.; McNamara, K.; Lee, I.
Utilization of synthetic peptides to evaluate the importance of substrate interaction at the proteolytic site of Escherichia coli Lon protease
Biochim. Biophys. Acta
1794
1355-1363
2009
Escherichia coli
Gur, E.; Sauer, R.T.
Recognition of misfolded proteins by Lon, a AAA(+) protease
Genes Dev.
22
2267-2277
2008
Escherichia coli
Griffith, K.L.; Fitzpatrick, M.M.; Keen, E.F.; Wolf, R.E.
Two functions of the C-terminal domain of Escherichia coli Rob: Mediating sequestration-dispersal as a novel off-on switch for regulating Robs activity as a transcription activator and preventing degradation of Rob by Lon protease
J. Mol. Biol.
388
415-430
2009
Escherichia coli
Heuveling, J.; Possling, A.; Hengge, R.
A role for Lon protease in the control of the acid resistance genes of Escherichia coli
Mol. Microbiol.
69
534-547
2008
Escherichia coli
Malik, M.; Capecci, J.; Drlica, K.
Lon protease is essential for paradoxical survival of Escherichia coli exposed to high concentrations of quinolone
Antimicrob. Agents Chemother.
53
3103-3105
2009
Escherichia coli
Duval, V.; Nicoloff, H.; Levy, S.B.
Combined inactivation of lon and ycgE decreases multidrug susceptibility by reducing the amount of OmpF porin in Escherichia coli
Antimicrob. Agents Chemother.
53
4944-4948
2009
Escherichia coli
Lin, Y.C.; Lee, H.C.; Wang, I.; Hsu, C.H.; Liao, J.H.; Lee, A.Y.; Chen, C.; Wu, S.H.
DNA-binding specificity of the Lon protease alpha-domain from Brevibacillus thermoruber WR-249
Biochem. Biophys. Res. Commun.
388
62-66
2009
Bacillus subtilis, Escherichia coli, Brevibacillus thermoruber, Brevibacillus thermoruber WR-249
Thomas, J.; Fishovitz, J.; Lee, I.
Utilization of positional isotope exchange experiments to evaluate reversibility of ATP hydrolysis catalyzed by Escherichia coli Lon protease
Biochem. Cell Biol.
88
119-128
2010
Escherichia coli
Liao, J.H.; Lin, Y.C.; Hsu, J.; Lee, A.Y.; Chen, T.A.; Hsu, C.H.; Chir, J.L.; Hua, K.F.; Wu, T.H.; Hong, L.J.; Yen, P.W.; Chiou, A.; Wu, S.H.
Binding and cleavage of E. coli HUbeta by the E. coli Lon protease
Biophys. J.
98
129-137
2010
Escherichia coli
Sakr, S.; Cirinesi, A.M.; Ullers, R.S.; Schwager, F.; Georgopoulos, C.; Genevaux, P.
Lon protease quality control of presecretory proteins in Escherichia coli and its dependence on the SecB and DnaJ (Hsp40) chaperones
J. Biol. Chem.
285
23506-23514
2010
Escherichia coli
Bissonnette, S.A.; Rivera-Rivera, I.; Sauer, R.T.; Baker, T.A.
The IbpA and IbpB small heat-shock proteins are substrates of the AAA+ Lon protease
Mol. Microbiol.
75
1539-1549
2010
Escherichia coli
Gur, E.; Sauer, R.T.
Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine
Proc. Natl. Acad. Sci. USA
106
18503-18508
2009
Escherichia coli
Li, M.; Gustchina, A.; Rasulova, F.S.; Melnikov, E.E.; Maurizi, M.R.; Rotanova, T.V.; Dauter, Z.; Wlodawer, A.
Structure of the N-terminal fragment of Escherichia coli Lon protease
Acta Crystallogr. Sect. D
66
865-873
2010
Escherichia coli (P0A9M0), Escherichia coli
Minami, N.; Yasuda, T.; Ishii, Y.; Fujimori, K.; Amano, F.
Regulatory role of cardiolipin in the activity of an ATP-dependent protease, Lon, from Escherichia coli
J. Biochem.
149
519-527
2011
Escherichia coli
Langklotz, S.; Narberhaus, F.
The Escherichia coli replication inhibitor CspD is subject to growth-regulated degradation by the Lon protease
Mol. Microbiol.
80
1313-1325
2011
Escherichia coli
Redelberger, D.; Genest, O.; Arabet, D.; Mejean, V.; Ilbert, M.; Iobbi-Nivol, C.
Quality control of a molybdoenzyme by the Lon protease
FEBS Lett.
587
3935-3942
2013
Escherichia coli
Wohlever, M.L.; Baker, T.A.; Sauer, R.T.
Roles of the N domain of the AAA+ Lon protease in substrate recognition, allosteric regulation and chaperone activity
Mol. Microbiol.
91
66-78
2014
Escherichia coli
Vieux, E.F.; Wohlever, M.L.; Chen, J.Z.; Sauer, R.T.; Baker, T.A.
Distinct quaternary structures of the AAA+ Lon protease control substrate degradation
Proc. Natl. Acad. Sci. USA
110
E2002-E2008
2013
Escherichia coli
Gur, E.; Vishkautzan, M.; Sauer, R.
Protein unfolding and degradation by the AAA+ Lon protease
Protein Sci.
21
268-278
2012
Escherichia coli
Andrianova, A.; Kudzhaev, A.; Serova, O.; Dergousova, N.; Rotanova, T.
Role of alpha-helical domains in functioning of ATP-dependent Lon protease of Escherichia coli
Russ. J. Bioorg. Chem.
40
620-627
2014
Escherichia coli
-
Kudzhaev, A.; Andrianova, A.; Dubovtseva, E.; Serova, O.; Rotanova, T.
Role of the inserted alpha-helical domain in E. coli ATP-dependent lon protease function
Acta Naturae
9
75-81
2017
Escherichia coli (P0A9M0), Escherichia coli
Pinti, M.; Gibellini, L.; Nasi, M.; De Biasi, S.; Bortolotti, C.A.; Iannone, A.; Cossarizza, A.
Emerging role of Lon protease as a master regulator of mitochondrial functions
Biochim. Biophys. Acta
1857
1300-1306
2016
Thermococcus onnurineus (B6YU74), Escherichia coli (P0A9M0), Saccharomyces cerevisiae (P36775), Homo sapiens (P36776), Mus musculus (Q8CGK3), Saccharomyces cerevisiae ATCC 204508 (P36775)
Fishovitz, J.; Sha, Z.; Chilakala, S.; Cheng, I.; Xu, Y.; Lee, I.
Utilization of mechanistic enzymology to evaluate the significance of ADP binding to human Lon protease
Front. Mol. Biosci.
4
47
2017
Escherichia coli (P0A9M0), Escherichia coli, Homo sapiens (P36776), Homo sapiens
Karlowicz, A.; Wegrzyn, K.; Gross, M.; Kaczynska, D.; Ropelewska, M.; Siemiatkowska, M.; Bujnicki, J.M.; Konieczny, I.
Defining the crucial domain and amino acid residues in bacterial Lon protease for DNA binding and processing of DNA-interacting substrates
J. Biol. Chem.
292
7507-7518
2017
Escherichia coli
Brown, B.L.; Vieux, E.F.; Kalastavadi, T.; Kim, S.; Chen, J.Z.; Baker, T.A.
N domain of the Lon AAA+ protease controls assembly and substrate choice
Protein Sci.
28
1239-1251
2018
Escherichia coli (P0A9M0), Escherichia coli
Arends, J.; Griego, M.; Thomanek, N.; Lindemann, C.; Kutscher, B.; Meyer, H.E.; Narberhaus, F.
An integrated proteomic approach uncovers novel substrates and functions of the Lon protease in Escherichia coli
Proteomics
18
e1800080
2018
Escherichia coli (P0A9M0), Escherichia coli
Kudzhaev, A.; Andrianova, A.; Serova, O.; Arkhipova, V.; Dubovtseva, E.; Rotanova, T.
The effect of mutations in the inserted domain of ATP-dependent Lon protease from E. coli on the enzyme function
Russ. J. Bioorg. Chem.
41
518-524
2015
Escherichia coli (P0A9M0), Escherichia coli
Spiridonova, V.; Kudzhaev, A.; Melnichuk, A.; Gainutdinov, A.; Andrianova, A.; Rotanova, T.
Interaction of DNA aptamers with the ATP-dependent Lon protease from Escherichia coli
Russ. J. Bioorg. Chem.
41
626-630
2015
Escherichia coli (P0A9M0)
Kudzhaev, A.; Dubovtseva, E.; Serova, O.; Andrianova, A.; Rotanova, T.
Effect of the deletion of the (173-280) fragment of the inserted alpha-helical domain on the functional properties of ATP-dependent Lon protease from E. coli
Russ. J. Bioorg. Chem.
44
518-527
2018
Escherichia coli (P0A9M0)
-
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