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Information on EC 3.4.25.2 - HslU-HslV peptidase
for references in articles please use BRENDA:EC3.4.25.2
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.25 Threonine endopeptidases
3.4.25.2 HslU-HslV peptidase
IUBMB Comments
The HslU subunit of the HslU—HslV complex functions as an ATP dependent ‘unfoldase’. The binding of ATP and its subsequent hydrolysis by HslU are essential for unfolding of protein substrates subsequently hydrolysed by HslV . HslU recognizes the N-terminal part of its protein substrates and unfolds these before they are guided to HslV for hydrolysis . In peptidase family T1.
The enzyme appears in viruses and cellular organisms
showSynonyms
atp-dependent protease, hsluv, clpyq, hslu atpase, hslv peptidase, hslvu protease, hslv protease, clpyq protease, hsluv complex, clpqy, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP-dependent protease hslV
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ClpQ
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ClpYQ
heat shock protein hslV
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HslU/HslV
HslUV
HslV
HslV peptidase
HslV protease
hslVU
HslVU protease
T01.006
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hslVU
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ATP-dependent protease consisting of two heat shock proteins, the HslU ATPase and HslV peptidase
hslVU
a two-component protease complex, which consists of the HslV peptidase and the HslU ATPase
HslVU protease
Q4Q116; Q4QI03
made of proteolytic (HslV) and regulatory (HslU) subunits
HslVU protease
Q4Q116; Q4QI03
made of proteolytic (HslV) and regulatory (HslU) subunits
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP-dependent cleavage of peptide bonds with broad specificity.
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ATP-dependent cleavage of peptide bonds with broad specificity.
model for a proteolytic cycle by HslVU protease, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
178303-43-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Arc mutant I137A + H2O
?
-
Substrates: monomeric mutant, degradation
Products: -
Products: -
?
Arc repressor + H2O
?
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Substrates: interaction of Arc substrates with HslU variants bearing mutations in the GYVG pore loop or the I domain, overview. N-terminal residues of Arc initially interact with the GYVG loop in the axial pore of HslU, while other portions of Arc contact disordered I-domain loops, residues 175-209, that project into the substrate-binding funnel above the pore
Products: -
Products: -
?
Arc-MYL-st11 + H2O
?
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Substrates: recombinant Arc fusion protein
Products: -
Products: -
?
Arc-MYL-st11 plus + H2O
?
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Substrates: recombinant Arc fusion protein
Products: -
Products: -
?
Arc-st11-ssrADD + H2O
?
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Substrates: Arc variants with a C-terminal ssrA tag (Arc-ssrA), the st11 tag and a mutant ssrA tag in which the terminal AA sequence is replaced by DD
Products: -
Products: -
?
Arc1-53-st11-titin-ssrA + H2O
?
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Substrates: recombinant truncated Arc fusion protein
Products: -
Products: -
?
benzyloxycarbonyl-EVNL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-EVNL + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
carbobenzoxy-Gly-Gly-Leu-7-amido-4-methyl coumarin + H2O
carbobenzoxy-Gly-Gly-Leu + 7-amino-4-methyl coumarin
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Substrates: the HslV peptidase alone shows a very weak peptidase activity towards carbobenzoxy-Gly-Gly-Leu-7-amido-4-methyl coumarin, but its activity increases 1-2 orders of magnitude when it binds to HslU in the presence of ATP
Products: -
Products: -
?
carbobenzoxy-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
carbobenzoxy-Gly-Gly-Leu + 7-amino-4-methylcoumarin
DnaA204-protein + H2O
?
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Substrates: the degradation of the DnaA204 protein contributes to the temperature sensitivity of the dna204 strain
Products: -
Products: -
?
fusion protein of SulA and maltose-binding protein + H2O
?
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Substrates: -
Products: -
Products: -
?
lambda CI repressor ext1-lambdacIN-RSEYE + H2O
?
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Substrates: -
Products: -
Products: -
?
lambda cI repressor mutant ext1-lambdacIN-ISVTL + H2O
?
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Substrates: a variant in which the C-terminal sequence is changed from RSEYE to ISVTL, to give ext1-lambdacIN-ISVTL, that HslUV degrades faster than the parental protein, ext1-lambdacIN-RSEYE, by 2fold increase in Vmax
Products: -
Products: -
?
N-carbobenzoxy-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
N-carbobenzoxy-Gly-Gly-Leu + 7-amino-4-methylcoumarin
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Substrates: -
Products: -
Products: -
?
N-carbobenzyloxy-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
N-carbobenzyloxy-Gly-Gly-Leu + 7-amino-4-methylcoumarin
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Substrates: -
Products: -
Products: -
?
puromycylpolypeptide + H2O
?
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Substrates: HslV and HslU interact and participate in the degradation of misfolded puromycylpolypeptides
Products: -
Products: -
?
RpoH + H2O
?
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Substrates: RpoH is a heat shock sigma transcription factor
Products: -
Products: -
?
unfolded lactalbumin + H2O
?
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Substrates: HslV alone can efficiently degrade certain unfolded proteins, such as unfolded lactalbumin and lysozyme prepared by complete reduction of disulfide bonds, but not their native forms. HslV alone cleaves a lactalbumin fragment sandwiched by two thioredoxin molecules, indicating that it can hydrolyze the internal peptide bonds of lactalbumin. Uncomplexed HslV is inactive under normal conditions, but can degrade unfolded proteins when the ATP level is low, as it is during carbon starvation
Products: -
Products: -
?
unfolded lysozyme + H2O
?
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Substrates: HslV alone can efficiently degrade certain unfolded proteins, such as unfolded lactalbumin and lysozyme prepared by complete reduction of disulfide bonds, but not their native forms. HslV alone cleaved a lactalbumin fragment sandwiched by two thioredoxin molecules, indicating that it can hydrolyze the internal peptide bonds of lactalbumin. Uncomplexed HslV is inactive under normal conditions, but can degrade unfolded proteins when the ATP level is low, as it is during carbon starvation
Products: -
Products: -
?
alpha-casein + H2O
?
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Substrates: interaction via HslV intact active site
Products: -
Products: -
?
alpha-casein + H2O
?
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Substrates: the structural features of the GYVG motif increase degrading activity
Products: -
Products: -
?
Arc + H2O
?
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Substrates: repressor protein, specific degradation, especially at heat shock temperatures, recognition of sequences near the N-terminus of Arc and strong binding requiring Mg2+ and ATP for degradation
Products: -
Products: -
?
Arc + H2O
?
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Substrates: N-terminal residues of Arc are important for HslUV degradation
Products: -
Products: -
?
Arc-st11-ssrA + H2O
?
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Substrates: Arc variants with a C-terminal ssrA tag (Arc-ssrA), the st11 and ssrA tags (Arc-st11-ssrA)
Products: -
Products: -
?
Arc-st11-ssrA + H2O
?
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Substrates: wild-type HslU binds this fluorescent substrate with an average affinity, whereas the Y91A mutant variant shows no detectable binding. Tyr91 side chain plays an important role in allowing HslU to bind Arc-st11-ssrA
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
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Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
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Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
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Substrates: HslV alone cleaves to a much lesser extent than in presence of HslU
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
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Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-GGL + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
?
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Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
?
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Substrates: the N-terminal Thr active sites of HslV are involved in the communication between HslV and HslU in addition to its role in the catalysis of peptide bond cleavage
Products: -
Products: -
?
carbobenzoxy-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
carbobenzoxy-Gly-Gly-Leu + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
carbobenzoxy-Gly-Gly-Leu-7-amido-4-methylcoumarin + H2O
carbobenzoxy-Gly-Gly-Leu + 7-amino-4-methylcoumarin
Substrates: The HslV peptidase alone shows a very weak peptidase activity towards carbobenzoxy-Gly-Gly-Leu-7-amido-4-methyl coumarin, but its activity increases 1-2 orders of magnitude when it binds to HslU in the presence of ATP
Products: -
Products: -
?
Insulin B-chain + H2O
?
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Substrates: HslVU degrades insulin B-chain even more rapidly in the presence of ATPgammaS than with ATP
Products: -
Products: -
?
RcsA + H2O
?
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Substrates: positive regulator of capsule transcription, RcsA
Products: -
Products: -
?
RcsA + H2O
?
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Substrates: specific substrate degradation, the enzyme is involved in regulation of RcsA, a capsule synthesis activator, the ClpYQ protease acts as a secondary protease in degrading the Lon protease substrate RscA
Products: -
Products: -
?
RcsA + H2O
?
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Substrates: specific substrate degradation, the enzyme is involved in regulation of RcsA, a capsule synthesis activator
Products: -
Products: -
?
succinyl-LLVY-7-amido-4-methylcoumarin + H2O
succinyl-LLVY + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
succinyl-LLVY-7-amido-4-methylcoumarin + H2O
succinyl-LLVY + 7-amino-4-methylcoumarin
Substrates: -
Products: -
Products: -
?
SulA + H2O
?
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Substrates: specific substrate degradation
Products: -
Products: -
?
SulA + H2O
?
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Substrates: specific substrate degradation, the substrate is a cell division inhibitor
Products: -
Products: -
?
SulA + H2O
?
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Substrates: recombinant substrate, produced as maltose-binding fusion protein and cleaved by factorXa
Products: -
Products: -
?
SulA + H2O
?
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Substrates: the double loops, i.e amino acids 137 to 150 and 175 to 209, in domain I of ClpY are necessary for initial recognition/tethering of natural substrates such as SulA, a cell division inhibitor protein
Products: -
Products: -
?
SulA + H2O
?
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Substrates: a cell division inhibitor protein. Degradation of MBP-SulA by ClpY and ClpY mutants Y408A and T87I in the presence of ClpQ
Products: -
Products: -
?
SulA + H2O
?
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Substrates: specific substrate degradation
Products: -
Products: -
?
SulA + H2O
?
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Substrates: specific substrate degradation, activities with SulA mutant protein substrates F10A, I37V, and P8L
Products: -
Products: -
?
SulA-maltose binding protein-fusion protein + H2O
?
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Substrates: recombinant substrate, formation of a ternary complex of HslV-HslU-substrate during reaction, molecular interaction study, interaction via HslU, not HslV
Products: -
Products: -
?
SulA-maltose binding protein-fusion protein + H2O
?
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Substrates: recombinant substrate, specific substrate degradation requires the flexibility provided by glycine residues and aromatic ring structures of the first 91 amino acids
Products: -
Products: -
?
TraJ + H2O
?
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Substrates: TraJ appears to be a substrate for HslVU throughout the growth cycle, but is protected or modified by a factor encoded by the F transfer region in the absence of stress. Activation of the Cpx regulon destabilizes the F plasmid transfer activator, TraJ, via the HslVU protease
Products: -
Products: -
?
additional information
?
-
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Substrates: no hydrolysis of gamma-globulin, lysozyme and bovine serum albumin
Products: -
Products: -
?
additional information
?
-
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Substrates: HslV and HslU can function together as a novel ATP-dependent protease, the HslVU protease. Pure HslV is a weak peptidase degrading certain hydrophobic peptides. HslU dramatically stimulates peptide hydrolysis by HslV when ATP is present. With a 1:4 molar ratio of HslV to HslU, approximately a 200fold increase in peptide hydrolysis is observed. HslV stimulates the ATPase activity of HslU 2-4fold. CTP and dATP are slowly hydrolyzed by HslU and allow some peptide hydrolysis
Products: -
Products: -
?
additional information
?
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Substrates: ATP-binding, but not its hydrolysis, is essential for assembly and proteolytic activity of HslVU
Products: -
Products: -
?
additional information
?
-
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Substrates: less than 1% of the activity with benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin is observed with succinyl-AAF-7-amido-4-methylcoumarin and succinyl-LLVY-7-amido-4-methylcoumarin. No activity with benzoyl-RGFFL-4-methoxy-beta-naphthylamide, glutaryl-AAA-4-methoxy-beta-naphthylamide, benzyloxycarbonyl-LLE-4-methoxy-beta-naphthylamide, succinyl-FLF-beta-naphthylamide, succinyl-LY-7-amido-4-methylcoumarin, benzoyl-GP-7-amido-4-methylcoumarin, acetyl-YVAA-7-amido-4-methylcoumarin, tert-butyloxycarbonyl-LRR-7-amido-4-methylcoumarin, t-butyloxycarbonyl-FVR-7-amido-4-methylcoumarin, benzoyl-GGR-7-amido-4-methylcoumarin, benzoyl-Arg-7-amido-4-methylcoumarin
Products: -
Products: -
?
additional information
?
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Substrates: hslV and hslU are coregulated. It is possible that ATPase HslU and protease HslV are involved in an ATP/GTP-dependent protein metabolism
Products: -
Products: -
?
additional information
?
-
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Substrates: the GYVG motif of HslU is important in unfolding of natively folded proteins as well as in translocation of unfolded proteins for degradation by HslV in its inner chamber
Products: -
Products: -
?
additional information
?
-
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Substrates: analysis of interaction of free and inhibited HslV with HslU showing moderate affinity, scheme of substrate-induced HslUV assemblage, overview
Products: -
Products: -
?
additional information
?
-
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Substrates: substrate binding, ATP-dependent protein degradation, and reaction mechanism, substrate engagement must occur after ATP-binding before HslUV unfolds the proteins, overview
Products: -
Products: -
?
additional information
?
-
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Substrates: degradation of proteins in an ATP-dependent and tag-specific manner. For degradation from the N-terminus, HslUV has the strongest unfolding ability of all the bacterial proteases (unfolding abilities of the 26S proteasome), whereas for degradation from the C-terminus, HslUV is one of the weaker unfoldases. HslUV unfolds proteins more effectively when degrading from the N- towards the C-terminus than in the opposite direction
Products: -
Products: -
?
additional information
?
-
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Substrates: HslVU is an ATP-dependent protease consisting of two heat shock proteins, the HslU ATPase and HslV peptidase. In the reconstituted enzyme, HslU stimulates the proteolytic activity of HslV by one to two orders of magnitude, while HslV increases the rate of ATP hydrolysis by HslU several-fold. HslV alone can efficiently degrade certain unfolded proteins, such as unfolded lactalbumin and lysozyme prepared by complete reduction of disulfide bonds, but not their native forms. HslV alone cleaves a lactalbumin fragment sandwiched by two thioredoxin molecules, indicating that it can hydrolyze the internal peptide bonds of lactalbumin. Uncomplexed HslV is inactive under normal conditions, but can degrade unfolded proteins when the ATP level is low, as it is during carbon starvation
Products: -
Products: -
?
additional information
?
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Substrates: ClpQ and ClpY are two heat shock proteins
Products: -
Products: -
?
additional information
?
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Substrates: in vivo, ClpYQ targets SulA, RcsA, RpoH, and TraJ molecules, identification of the molecular determinants required for the binding of its natural protein substrates by yeast two-hybrid analysis. Domain I of ClpY contains the residues, amino acids 137-150 of loop 1 and 175-209 of loop 2, double loops in domain I of ClpY, that are responsible for recognition of its natural substrates, while domain C is necessary to engage ClpQ, overview
Products: -
Products: -
?
additional information
?
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Substrates: ClpYQ is a two-component ATP-dependent protease in which ClpQ is the peptidase subunit and ClpY is the ATPase and the substrate-binding subunit. The ATP-dependent proteolysis is mediated by substrate recognition in the ClpYQ complex
Products: -
Products: -
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additional information
?
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Substrates: HslVU is a bacterial ATP-dependent protease consisting of hexameric HslU ATPase and dodecameric HslV protease. HslV uses the N-terminal threonine as the active site residue. HslV has 12 active sites among the 14beta-subunits that can potentially contribute to proteolytic activity, but only 6 active sites are sufficient to support full catalytic activity. Substrate-mediated stabilization of the HslV-HslU interaction
Products: -
Products: -
?
additional information
?
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Substrates: HslU hexamers recognize and unfold native protein substrates and then translocate the polypeptide into the degradation chamber of the HslV peptidase. The degradation appears to consist of discrete steps, which involve the interaction of different terminal sequence signals in the substrate with different receptor sites in the HslUV protease. Mutations in the unstructured N-terminal and C-terminal sequences of two model substrates alter HslUV recognition and degradation kinetics, including changes in Vmax. Blocking either terminus of the substrate interferes with HslUV degradation, with synergistic effects when both termini are obstructed
Products: -
Products: -
?
additional information
?
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Substrates: modeling of overall reaction by substrate binding and dissociation steps, and by a rate-limiting enzymatic step, which corresponds to substrate engagement, unfolding, or translocation
Products: -
Products: -
?
additional information
?
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Substrates: substrates are typically targeted to specific AAA+ proteases by peptide sequences. In the AAA+ HslUV protease, substrates are bound and unfolded by a ring hexamer of HslU, before translocation through an axial pore and into the HslV degradation chamber. The I domain plays an active role in coordinating substrate binding, ATP hydrolysis, and protein degradation by the HslUV proteolytic machine
Products: -
Products: -
?
additional information
?
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Substrates: the enzyme degrades only the SulA moiety of recombinant fusion proteins, the fused proteins, e.g. the green fluorescent protein, are not hydrolyzed
Products: -
Products: -
?
additional information
?
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Substrates: degradation of proteins in an ATP-dependent and tag-specific manner. For degradation from the N-terminus, HslUV has the strongest unfolding ability of all the bacterial proteases (unfolding abilities of the 26S proteasome), whereas for degradation from the C-terminus, HslUV is one of the weaker unfoldases. HslUV unfolds proteins more effectively when degrading from the N- towards the C-terminus than in the opposite direction
Products: -
Products: -
?
additional information
?
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Substrates: the HslUV complex is an assembly of heat shock locus gene products U and V. The formation of the complete complex is essential for the proteasome to carry out its biochemical and physiological role in the parasite, namely to degrade specific target proteins in an ATP-dependent chaperone assisted manner
Products: -
Products: -
?
additional information
?
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Substrates: ClpYQ plays a minor role in stress survival and is required for growth at high temperature of 45Ā°C
Products: -
Products: -
?
SulA + H2O
additional information
-
-
Substrates: -
Products: the enzyme produces 58 peptides with various sizes, 3-31 residues
Products: the enzyme produces 58 peptides with various sizes, 3-31 residues
?
SulA + H2O
additional information
-
-
Substrates: the central and the C-terminal regions are preferentially cleaved. Major cleavage sites: Ala80-Ser81, Ala150-Ser151, Leu54-Gln55, Ile163-His164, Leu67-Thr68, Leu49-Leu50, Leu65-Trp66. No cleavage in absence of ATP
Products: the enzyme produces 58 peptides with various sizes, 3-31 residues
Products: the enzyme produces 58 peptides with various sizes, 3-31 residues
?
SulA + H2O
additional information
-
-
Substrates: cell division inhibitor SulA, the internal region of SulA is necessary for interactions with ClpY, the N-terminal amino acid residues of SulA are not necessary
Products: -
Products: -
?
SulA + H2O
additional information
-
-
Substrates: hslVU in addition to Lon plays an important role in regulation of cell division through degradation of SulA
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Arc + H2O
?
-
Substrates: N-terminal residues of Arc are important for HslUV degradation
Products: -
Products: -
?
DnaA204-protein + H2O
?
-
Substrates: the degradation of the DnaA204 protein contributes to the temperature sensitivity of the dna204 strain
Products: -
Products: -
?
lambda CI repressor ext1-lambdacIN-RSEYE + H2O
?
-
Substrates: -
Products: -
Products: -
?
puromycylpolypeptide + H2O
?
-
Substrates: HslV and HslU interact and participate in the degradation of misfolded puromycylpolypeptides
Products: -
Products: -
?
RcsA + H2O
?
-
Substrates: specific substrate degradation, the enzyme is involved in regulation of RcsA, a capsule synthesis activator, the ClpYQ protease acts as a secondary protease in degrading the Lon protease substrate RscA
Products: -
Products: -
?
TraJ + H2O
?
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Substrates: TraJ appears to be a substrate for HslVU throughout the growth cycle, but is protected or modified by a factor encoded by the F transfer region in the absence of stress. Activation of the Cpx regulon destabilizes the F plasmid transfer activator, TraJ, via the HslVU protease
Products: -
Products: -
?
SulA + H2O
?
-
Substrates: specific substrate degradation
Products: -
Products: -
?
SulA + H2O
?
-
Substrates: the double loops, i.e amino acids 137 to 150 and 175 to 209, in domain I of ClpY are necessary for initial recognition/tethering of natural substrates such as SulA, a cell division inhibitor protein
Products: -
Products: -
?
SulA + H2O
?
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Substrates: specific substrate degradation
Products: -
Products: -
?
additional information
?
-
Substrates: hslV and hslU are coregulated. It is possible that ATPase HslU and protease HslV are involved in an ATP/GTP-dependent protein metabolism
Products: -
Products: -
?
additional information
?
-
-
Substrates: the GYVG motif of HslU is important in unfolding of natively folded proteins as well as in translocation of unfolded proteins for degradation by HslV in its inner chamber
Products: -
Products: -
?
additional information
?
-
-
Substrates: ClpQ and ClpY are two heat shock proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: in vivo, ClpYQ targets SulA, RcsA, RpoH, and TraJ molecules, identification of the molecular determinants required for the binding of its natural protein substrates by yeast two-hybrid analysis. Domain I of ClpY contains the residues, amino acids 137-150 of loop 1 and 175-209 of loop 2, double loops in domain I of ClpY, that are responsible for recognition of its natural substrates, while domain C is necessary to engage ClpQ, overview
Products: -
Products: -
?
additional information
?
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Substrates: HslU hexamers recognize and unfold native protein substrates and then translocate the polypeptide into the degradation chamber of the HslV peptidase. The degradation appears to consist of discrete steps, which involve the interaction of different terminal sequence signals in the substrate with different receptor sites in the HslUV protease. Mutations in the unstructured N-terminal and C-terminal sequences of two model substrates alter HslUV recognition and degradation kinetics, including changes in Vmax. Blocking either terminus of the substrate interferes with HslUV degradation, with synergistic effects when both termini are obstructed
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additional information
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Substrates: the HslUV complex is an assembly of heat shock locus gene products U and V. The formation of the complete complex is essential for the proteasome to carry out its biochemical and physiological role in the parasite, namely to degrade specific target proteins in an ATP-dependent chaperone assisted manner
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additional information
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Substrates: ClpYQ plays a minor role in stress survival and is required for growth at high temperature of 45Ā°C
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Products: -
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SulA + H2O
additional information
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Substrates: -
Products: the enzyme produces 58 peptides with various sizes, 3-31 residues
Products: the enzyme produces 58 peptides with various sizes, 3-31 residues
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SulA + H2O
additional information
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Substrates: hslVU in addition to Lon plays an important role in regulation of cell division through degradation of SulA
Products: -
Products: -
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenosine 5'-(alpha,beta-methylene)triphosphate
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HslVU degrades insulin B-chain more rapidly in the presence of ATPgammaS than with ATP
ATPgammaS
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HslVU degrades insulin B-chain more rapidly in the presence of ATPgammaS than with ATP
beta,gamma-Imido-ATP
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supports proteolytic activity to an extent less than 10% of that seen with ATP
5'-adenylyl beta,gamma-imidotriphosphate
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the enzyme degrades SulA and the fusion protein of SulA and maltose-binding protein in presence of ATP but not with ATPgammaS
5'-adenylyl beta,gamma-imidotriphosphate
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can support peptide hydrolysis, but only after an initial time lag not seen with ATP. This delay decreases at higher temperatures and with higher HslV or HslU concentrations and is eliminated by preincubation of HslV and HslU together
5'-adenylyl beta,gamma-imidotriphosphate
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can support peptide hydrolysis, but only after an initial time lag not seen with ATP. This delay decreases at higher temperatures and with higher HslV or HslU concentrations and is eliminated by preincubation of HslV and HslU together. Supports hydrolysis of casein and other polypeptides only 20% as well as ATP. But in presence of K+, Cs+ or NH4+, activation of casein degradation is even better than that by ATP, although it is not hydrolyzed
ATP
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ATP-binding, but not its hydrolysis, is essential for assembly and proteolytic activity of HslVU. The ability of ATP and its analogs in supporting the proteolytic activity is closely correlated with their ability in supporting the oligomerization of HslU and the formation of the HslVU complex
ATP
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ATP activates hydrolysis of benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin 150fold
ATP
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HslV and HslU can function together as a novel ATP-dependent protease, the HslVU protease. Pure HslV is a weak peptidase degrading certain hydrophobic peptides. HslU dramatically stimulates peptide hydrolysis by HslV when ATP is present. With a 1:4 molar ratio of HslV to HslU, approximately a 200fold increase in peptide hydrolysis is observed. HslV stimulates the ATPase activity of HslU 2-4fold. CTP and dATP are slowly hydrolyzed by HslU and allow some peptide hydrolysis
ATP
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the enzyme degrades SulA and the fusion protein of SulA and maltose-binding protein in presence of ATP but not with ATPgammaS
ATP
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HslV can slowly hydrolyze insulin B-chain, casein or carboxymethylated lactalbumin, but its activity is stimulated 20fold by HslU in presence of ATP
ATP
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ATP concentrations that activate hydrolysis of benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin are 50-100fold lower than those necessary for degradation of proteins, e.g. casein. ATP binding to a high affinity site triggers the formation of an active state capable of peptide cleavage, although ATP hydrolysis facilitates this process
ATP
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ATP binding and hydrolysis are critical for protein degradation by HslUV, an AAA+ machine containing one or two HslU ATPases and the HslV peptidase. Asymmetric mechanism of ATP binding and hydrolysis. Molecular contacts between HslU and HslV vary dynamically throughout the ATPase cycle. Nucleotide binding controls HslUV assembly and activity. Binding of a single ATP allows HslU to bind HslV, whereas additional ATPs must bind HslU to support substrate recognition and to activate ATP hydrolysis, which powers substrate unfolding and translocation
ATP
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dependent on, an ATP-binding site in domain N, separate from its role in polypeptide, ClpY, oligomerization, is required for complex formation with ClpQ
ATP
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dependent on. The intermediate domain of HslU is required for robust ATP hydrolysis, ATP hydrolysis activities of wild-type and mutant enzymes, overview
additional information
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HslU requires Mg2+ together with ATP for activity
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additional information
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HslU does not hydrolyze ATPgammaS, an ATP analogue
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additional information
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no activity with ATP-gammaS analogue, thermodynamic analysis of ATP-gammaS-binding and ATPase activity of wild-type ClpY and its T87I mutant, overview. In the presence of MBP-SulA and ClpQ, the mutant has about one-fourth of the ATPase activity of wild-type ClpY, ClpY mutant T87I in its hexameric form is defective in ATPase activity
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CaCl2
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allows some peptidase and caseinase activity in the absence of any nucleotide, however Ca2+ abolishes ATP hydrolysis and prevents further activation by ATP and 5'-adenylyl beta,gamma-imidodiphosphate
Cs+
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stimulates 4-6fold the peptidase activity with 5'-adenylyl beta,gamma-imidodiphosphate present and eliminates the time lag for activation, no stimulatory effect with ATP
KCl
Mg2+
MgCl2
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allows some peptidase and caseinase activity in the absence of any nucleotide
MnCl2
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allows some peptidase and caseinase activity in the absence of any nucleotide, however Mn2+ abolishes ATP hydrolysis and prevents further activation by ATP and 5'-adenylyl beta,gamma-imidodiphosphate
NH4+
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stimulates 4-6fold the peptidase activity with 5'-adenylyl beta,gamma-imidodiphosphate present and eliminates the time lag for activation, no stimulatory effect with ATP
KCl
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stimulates 4-6fold the peptidase activity with 5'-adenylyl beta,gamma-imidodiphosphate present and eliminates the time lag for activation, no stimulatory effect with ATP
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
benzyloxycarbonyl-Ile-Glu(tert-butyl)-Ala-Leu-al
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0.001 mM, almost complete inhibition of peptidase activity, no inhibition of hydrolysis of insulin B-chain or other polypeptide substrates
benzyloxycarbonyl-Leu-Leu-norvalinal
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0.004 mM, inhibits hydrolysis of both benzyloxycarbonyl-GGL-7-amido-4-methylcoumarin and insulin B-chain to a similar extent
NLVS
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in the presence of ATP, the proteasome inhibitor markedly increases the interaction between HslV and HslU and causes the activation of the HslU ATPase
ATP
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inhibits the degradation of unfolded proteins by HslV. This inhibitory effect of ATP is markedly diminished by substitution of the Arg86 residue located in the apical pore of HslV with Gly, suggesting that interaction of ATP with the Arg residue blocks access of unfolded proteins to the proteolytic chamber of HslV
lactacystin
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irreversible, much greater inhibition of the degradation of insulin B-chain than on peptide hydrolysis
lactacystin
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in the presence of ATP, the proteasome inhibitor markedly increases the interaction between HslV and HslU and causes the activation of the HslU ATPase
NEM
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preincubation with followed by inactivation of dithiothreitol causes inhibition of peptide hydrolysis
additional information
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the I125-labeled nitrophenyl derivative 125iodo-NIP-Leu-Leu-Leu vinyl sulfone covalently modifies and inhibits HslV, but only in presence of HslU and ATP
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additional information
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enzyme inactivation by 7.5% SDS and 10% v/v 2-mercaptoethanol
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additional information
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protein binding, e.g. of Escherichia coli ClpS, SspB, or DegS PDZ domain polypeptides, to the C-terminus of substrates selectively slows HslUV degradation, the inhibition affects an early step in degradation. Synergistic effects of N- and C-terminal blocking
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additional information
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PSI, a classical proteasome inhibitor, does not influence the co-expression level of HslV and proteasome 20 in strain Be-78; PSI, a classical proteasome inhibitor, influences the co-expression level of HslV and proteasome 20 in strain Be-62
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-{(E)-[(2-hydroxynaphthalen-1-yl)methylidene]amino}-2-(4-nitrophenyl)quinazolin-4(3H)-one
HslU