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Information on EC 3.4.21.12 - alpha-lytic endopeptidase and Organism(s) Lysobacter enzymogenes and UniProt Accession P00778
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3.4.21.12 alpha-lytic endopeptidaseSpecify your search results
The taxonomic range for the selected organisms is: Lysobacter enzymogenes
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
preferential cleavage: Ala-/-, Val-/- in bacterial cell walls, elastin and other proteins
Synonyms
protein l5, alpha-lytic protease, alphalp, alpha-lytic proteinase, bacteriolytic protease l5, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Alpha-lytic endopeptidase
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alpha-lytic protease
alpha-lytic proteinase
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Mycobacterium sorangium alpha-lytic proteinase
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Myxobacter 495 alpha-lytic proteinase
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Myxobacter alpha-lytic proteinase
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proteinase, Mycobacterium sorangium alpha-lytic
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proteinase, Myxobacter alpha-lytic
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alpha-lytic protease
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
preferential cleavage: Ala-/-, Val-/- in bacterial cell walls, elastin and other proteins
the specificity mechanism of the enzyme is influenced by dynamic motion around the S1 binding pocket in addition to the static structural characteristics
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CAS REGISTRY NUMBER
COMMENTARY
37288-76-9
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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
N-succinyl-L-Ala-L-Ala-L-Ala 4-nitroanilide + H2O
N-succinyl-L-Ala-L-Ala-L-Ala + 4-nitroaniline
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?
succinyl-Ala-Ala-Pro-Ala-4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Ala + 4-nitroaniline
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high activity with wild-type enzyme and mutant enzyme M190A
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?
succinyl-Ala-Ala-Pro-Leu-4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Leu + 4-nitroaniline
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weak activity with wild-type enzyme, high activity with mutant enzyme M190A
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?
succinyl-Ala-Ala-Pro-Phe-4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Phe + 4-nitroaniline
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weak activity with wild-type enzyme, high activity with mutant enzyme M190A
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?
succinyl-Ala-Ala-Pro-Val-4-nitroanilide + H2O
succinyl-Ala-Ala-Pro-Val + 4-nitroaniline
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high activity with wild-type enzyme and mutant enzyme M190A
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?
succinyl-Ala-Ala-Pro-X-p-nitroanilide + H2O
?
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X: Gly, Thr, Val, Leu, Ile, Met, Phe
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?
additional information
?
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oligopeptides on the carbonyl side of amino acids with short neutral aliphatic side-chains
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?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
guanidine hydrochloride
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1% residual activity in the presence of 4 mM guanidine hydrochloride
methoxysuccinyl-Ala-Ala-Pro-L-boroPhe
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the carboxylate of the C-terminal amino acid residue is replaced with B(OH)2. Boron-11 pure quadrupole resonance investigation indicates close to tetrahedral boron coordination in the active site of the enzyme/inhibitor complex
methoxysuccinyl-Ala-Ala-Pro-L-boroVal
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the carboxylate of the C-terminal amino acid residue is replaced with B(OH)2. Boron-11 pure quadrupole resonance investigation indicates tetrahedral boron coordination in the active site of the enzyme/inhibitor complex
N-terminal 166 amino acid Pro region of alpha-lytic protease
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dual role of folding and inhibition
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Turkey ovomucoid third domain
OMTKY3, very weak inhibitor, different mutations in the inhibitory protein are found to affect the inhibitory effect
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Turkey ovomucoid third domain
Turkey Ovomucoid Third Domain (OMTKY3) inhibits the enzyme much more weakly (by about 1000000times) than eglin C. A variant of OMTKY3 with five mutations K13A/P14E/L18A/R21T/N36D inhibits 10000times more strongly than the wild type inhibitor
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additional information
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lyophilization induces a structural change in the enzyme that is not reversed by redissolution in water. The structural change reduces the mobility of the active-site histidine residue and the catalytic activity of the enzyme. The application of mild pressure to solutions of the altered enzyme reverses the lyophilization-induced structural change and restores the mobility of the histidine residue and the enzyme's catalytic activity
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
sodium deoxycholate
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196% activity in the presence of 0.1% (w/v) sodium deoxycholate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
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the enzyme is synthesized with a 166 amino acid pro region that catalyzes the folding of the 198 amino acid protease into its native conformation.
proteolytic modification
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the enzyme is synthesized with a large, two-domain pro region (Pro) that catalyzes the folding of the protease to its native conformation. In the absence of its (Pro) folding catalyst, alpha-lytic protease encounters a very large folding barrier that effectively prevents the protease from folding. The extremely high alpha-lytic protease folding barrier necessitates the presence of both the (Pro) domains
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
subangstrom crystallography reveals that short ionic hydrogen bonds, and not a His-Asp low-barrier hydrogen bond, stabilize the transition state in serine protease catalysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G216A
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216F
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216G
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216H
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216I
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216L
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216Q
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216S
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216T
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216V
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216W
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
G216Y
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active enzyme, but production levels for the mutants with larger substitutions do decrease significantly
M190A
additional information
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Pro region N-domain mutants: disruption of the hydrogen bonding potentials of Y26 and E30 primarily alters Pro binding to the folding transition state as compared to binding in the initial and native state complexes
M190A
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mutation broadens specificity while maintaining or increasing catalytic activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
kinetic stability impaired by the large, cooperative unfolding barrier plays a critical role in extending the lifetime of the protease in its harsh environment
alpha-lytic protease can exist in two separately stable conformations with different His57 mobilities and catalytic activities
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lyophilization induces a structural change in the enzyme that is not reversed by redissolution in water. The structural change reduces the mobility of the active-site histidine residue and the catalytic activity of the enzyme. The application of mild pressure to solutions of the altered enzyme reverses the lyophilization-induced structural change and restores the mobility of the histidine residue and the enzyme's catalytic activity
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Pro N-domain both provides direct interactions with alpha-lytic protease that stabilize the folding transition state and confers stability to the Pro C-domain
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant enzyme precursor with a pro region lacking its last three amino acids: the turnover number of folding of the mutant enzyme is 1000fold lower that for the folding of the wild type enzyme. Mutant enzyme precursor with a pro region lacking its last three amino acids and two additional mutations, R102H and G134S: turnover number of folding of the mutant enzyme is 2fold higher than that of the wild-type enzyme
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bone, R.; Shenvi, A.B.; Kettner, C.A.; Agard, D.A.
Serine protease mechanism: structure of an inhibitory complex of alpha-lytic protease and a tightly bound peptide boronic acid
Biochemistry
26
7609-7614
1987
Lysobacter enzymogenes
Fujinaga, M.; delBaere, L.T.J.; Brayer, G.D.; James, M.N.G.
Refined structure of alpha-lytic protease at 1.7 A resolution. Analysis of hydrogen bonding and solvent structure
J. Mol. Biol.
184
479-502
1985
Lysobacter enzymogenes
Bachovchin, W.W.; Kaiser, R.; Richards, J.H.; Roberts, J.D.
Catalytic mechanism of serine proteases: reexamination of the pH dependence of the histidyl 1J13C2-H coupling constant in the catalytic triad of alpha-lytic protease
Proc. Natl. Acad. Sci. USA
78
7323-7326
1981
Lysobacter enzymogenes
Davis, J.H.; Agard, D.A.
Relationship between enzyme specificity and the backbone dynamics of free and inhibited alpha-lytic protease
Biochemistry
37
7696-7707
1998
Lysobacter enzymogenes
Sohl, J.L.; Shiau, A.K.; Rader, S.D.; Wilk, B.J.; Agard, D.A.
Inhibition of alpha-lytic protease by pro region C-terminal steric occlusion of the active site
Biochemistry
36
3894-3902
1997
Lysobacter enzymogenes
Mace, J.E.; Agard, D.A.
Kinetic and structural characterization of mutations of glycine 216 in alpha-lytic protease: a new target for engineering substrate specificity
J. Mol. Biol.
254
720-736
1995
Lysobacter enzymogenes
Bone, R.; Sampson, N.S.; Bartlett, P.A.; Agard, D.A.
Crystal structures of alpha-lytic protease complexes with irreversibly bound phosphonate esters
Biochemistry
30
2263-2272
1991
Lysobacter enzymogenes
Ivanov, D.; Bachovchin, W.W.; Redfield, A.G.
Boron-11 pure quadrupole resonance investigation of peptide boronic acid inhibitors bound to alpha-lytic protease
Biochemistry
41
1587-1590
2002
Lysobacter enzymogenes
Cunningham, E.L.; Mau, T.; Truhlar, S.M.; Agard, D.A.
The pro region N-terminal domain provides specific interactions required for catalysis of alpha-lytic protease folding
Biochemistry
41
8860-8867
2002
Lysobacter enzymogenes
Fuhrmann, C.N.; Kelch, B.A.; Ota, N.; Agard, D.A.
The 0.83 A resolution crystal structure of alpha-lytic protease reveals the detailed structure of the active site and identifies a source of conformational strain
J. Mol. Biol.
338
999-1013
2004
Lysobacter enzymogenes (P00778)
Derman, A.I.; Agard, D.A.
Two energetically disparate folding pathways of alpha-lytic protease share a single transition state
Nat. Struct. Biol.
7
394-397
2000
Lysobacter enzymogenes
Ota, N.; Agard, D.A.
Enzyme specificity under dynamic control II: Principal component analysis of alpha-lytic protease using global and local solvent boundary conditions
Protein Sci.
10
1403-1414
2001
Lysobacter enzymogenes
Fuhrmann, C.N.; Daugherty, M.D.; Agard, D.A.
Subangstrom crystallography reveals that short ionic hydrogen bonds, and not a His-Asp low-barrier hydrogen bond, stabilize the transition state in serine protease catalysis
J. Am. Chem. Soc.
128
9086-9102
2006
Lysobacter enzymogenes (P00778)
Haddad, K.C.; Sudmeier, J.L.; Bachovchin, D.A.; Bachovchin, W.W.
alpha-Lytic protease can exist in two separately stable conformations with different His57 mobilities and catalytic activities
Proc. Natl. Acad. Sci. USA
102
1006-1011
2005
Lysobacter enzymogenes
Qasim, M.A.; Van Etten, R.L.; Yeh, T.; Saunders, C.; Ganz, P.J.; Qasim, S.; Wang, L.; Laskowski, M.
Despite having a common P1 Leu, eglin C inhibits alpha-lytic proteinase a million-fold more strongly than does turkey ovomucoid third domain
Biochemistry
45
11342-11348
2006
Lysobacter enzymogenes (P00778)
Deng, N.J.; Cieplak, P.
Insights into affinity and specificity in the complexes of alpha-lytic protease and its inhibitor proteins: binding free energy from molecular dynamics simulation
Phys. Chem. Chem. Phys.
11
4968-4981
2009
Lysobacter enzymogenes (P00778)
Salimi, N.L.; Ho, B.; Agard, D.A.
Unfolding simulations reveal the mechanism of extreme unfolding cooperativity in the kinetically stable alpha-lytic protease
PLoS Comput. Biol.
6
e1000689
2010
Lysobacter enzymogenes
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