EzCatDB: S00295
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DB codeS00295
RLCP classification1.13.30000.9 : Hydrolysis
CATH domainDomain 13.40.50.200 : Rossmann foldCatalytic domain
E.C.3.4.21.64

CATH domainRelated DB codes (homologues)
3.40.50.200 : Rossmann foldS00296,D00219,S00519

Enzyme Name
UniProtKBKEGG

P06873
Protein nameProteinase Kpeptidase K
Tritirachium alkaline proteinase
Tritirachium album serine proteinase
proteinase K
Tritirachium album proteinase K
endopeptidase K
SynonymsEC 3.4.21.64
Tritirachium alkaline proteinase
Endopeptidase K
MEROPSS08.054 (Serine)
PfamPF05922 (Inhibitor_I9)
PF00082 (Peptidase_S8)
[Graphical view]


UniProtKB:Accession NumberP06873
Entry namePRTK_TRIAL
ActivityHydrolysis of keratin, and of other proteins with subtilisin-like specificity. Hydrolyzes peptide amides.
Subunit
Subcellular location
CofactorBinds 2 calcium ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00012C00001C00017C00012I00087I00085I00086
CompoundProteinPeptideH2OProteinPeptidePeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein


ChEBI

15377





PubChem

962
22247451





                
1bjrEUnboundBound:VAL-ALA-GLN-GLY-GLY-ALA-ALA-GLY-LEU-ALA UnboundUnboundUnboundUnboundUnbound
1egqAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1ic6AUnboundUnbound UnboundUnboundUnboundUnboundUnbound
1pekEUnboundUnbound Bound:PRO-ALA-PRO-PHE(chain C)Bound:ALA-ALA(chain D)UnboundUnboundUnbound
1ptkAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
2pkcAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
2prkAUnboundUnbound UnboundUnboundUnboundUnboundUnbound
3prkEUnboundUnbound UnboundUnboundUnboundUnboundTransition-state-analogue:MSU-ALA-ALA-PRO-ALA-CH2

Active-site residues
resource
Swiss-prot;P06873 & PDB;1pek, 1ptk
pdbCatalytic residuesMain-chain involved in catalysis
          
1bjrEASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
1egqAASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
1ic6AASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
1pekEASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
1ptkAASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
2pkcAASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
2prkAASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224
3prkEASP 39;HIS 69;ASN 161;THR 223;SER 224
SER 224

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.8, p.164-1683

references
[1]
CommentsX-ray crystallography
Medline ID84261419
PubMed ID6378621
JournalEMBO J
Year1984
Volume3
Pages1311-4
AuthorsPaehler A, Banerjee A, Dattagupta JK, Fujiwara T, Lindner K, Pal GP, Suck D, Weber G, Saenger W
TitleThree-dimensional structure of fungal proteinase K reveals similarity to bacterial subtilisin.
Related UniProtKBP06873
[2]
CommentsX-ray crystallography (1.5 Angstroms)
PubMed ID3271105
JournalActa Crystallogr B
Year1988
Volume44
Pages163-72
AuthorsBetzel C, Pal GP, Saenger W
TitleSynchrotron X-ray data collection and restrained least-squares refinement of the crystal structure of proteinase K at 1.5 A resolution.
Related PDB2prk
[3]
CommentsX-ray crystallography (1.5 Angstroms)
PubMed ID3203685
JournalEur J Biochem
Year1988
Volume178
Pages155-71
AuthorsBetzel C, Pal GP, Saenger W
TitleThree-dimensional structure of proteinase K at 0.15-nm resolution.
Related PDB1ptk
[4]
CommentsX-ray crystallography (2.2 Angstroms)
PubMed ID1894649
JournalJ Biol Chem
Year1991
Volume266
Pages17695-9
AuthorsWolf WM, Bajorath J, Muller A, Raghunathan S, Singh TP, Hinrichs W, Saenger W
TitleInhibition of proteinase K by methoxysuccinyl-Ala-Ala-Pro-Ala-chloromethyl ketone. An x-ray study at 2.2-A resolution.
Related PDB3prkE
[5]
CommentsX-ray crystallography (2.2 Angstroms)
PubMed ID8340410
JournalJ Biol Chem
Year1993
Volume268
Pages15854-8
AuthorsBetzel C, Singh TP, Visanji M, Peters K, Fittkau S, Saenger W, Wilson KS
TitleStructure of the complex of proteinase K with a substrate analogue hexapeptide inhibitor at 2.2-A resolution.
Related PDB1pekE
[6]
CommentsX-ray crystallography (1.5 Angstroms)
PubMed ID8083213
JournalJ Biol Chem
Year1994
Volume269
Pages23108-11
AuthorsMuller A, Hinrichs W, Wolf WM, Saenger W
TitleCrystal structure of calcium-free proteinase K at 1.5-A resolution.
Related PDB2pkc
Related UniProtKBP06873
[7]
CommentsX-ray crystallography (2.44 Angstroms)
Medline ID98412873
PubMed ID9741842
JournalProteins
Year1998
Volume33
Pages30-8
AuthorsSingh TP, Sharma S, Karthikeyan S, Betzel C, Bhatia KL
TitleCrystal structure of a complex formed between proteolytically-generated lactoferrin fragment and proteinase K.
Related PDB1bjrE
Related UniProtKBP06873
[8]
CommentsX-ray crystallography (2.2 Angstroms)
PubMed ID10737944
JournalProteins
Year2000
Volume39
Pages226-34
AuthorsGupta MN, Tyagi R, Sharma S, Karthikeyan S, Singh TP
TitleEnhancement of catalytic efficiency of enzymes through exposure to anhydrous organic solvent at 70 degrees C. Three-dimensional structure of a treated serine proteinase at 2.2 A resolution.
Related PDB1cnm
[9]
CommentsX-ray crystallography (0.98 Angstroms)
PubMed ID11258922
JournalBiochemistry
Year2001
Volume40
Pages3080-8
AuthorsBetzel C, Gourinath S, Kumar P, Kaur P, Perbandt M, Eschenburg S, Singh TP
TitleStructure of a serine protease proteinase K from Tritirachium album limber at 0.98 A resolution.
Related PDB1ic6A
[10]
CommentsX-ray crystallography, catalysis
PubMed ID11563328
JournalIndian J Biochem Biophys
Year2001
Volume38
Pages34-41
AuthorsSharma S, Tyagi R, Gupta MN, Singh TP
TitleEnhancement of catalytic activity of enzymes by heating in anhydrous organic solvents: 3D structure of a modified serine proteinase at high resolution.
[11]
CommentsX-ray crystallography (1.5 Angstroms)
PubMed ID11438752
JournalProtein Eng
Year2001
Volume14
Pages307-13
AuthorsSingh RK, Gourinath S, Sharma S, Roy I, Gupta MN, Betzel C, Srinivasan A, Singh TP
TitleEnhancement of enzyme activity through three-phase partitioning: crystal structure of a modified serine proteinase at 1.5 A resolution.
Related PDB1egq

comments
This enzyme belongs to the peptidase family-S8.
This enzyme, protenase K, also has a catalytic triad (Asp/His/Ser), which is the same as those of other serine proteases, such as chymotrypsin, trypsin and subtilisin.
The paper [3] proposed a possible catalytic mechanism for this proteinase K, as follows:
In the catalytic center, the oxyanion hole is occupied by a water molecule, and the substrate-recognition site is close to the center. A substrate peptide enters the active site, is attacked by the sidechain of Ser224 and the negative charge of the resulting tetrahedral hemiketal transition sate is stabilized by hydrogen-bond formation in the oxyanion hole. The leaving group of R-NH2 (product 1) leaves the active site and the acyl-enzyme formed is hydrolysed by a water molecule. The product-2 formed diffuses out of the substrate-recognition site and the oxyanion hole is filled by another water molecule [3].
However, in contrast to other trypsin-like serine proteases, the oxyanion hole is composed of sidechains of Asn161 and Thr223, as well as mainchain amide of Ser224, as in subtilisin (D00219 in EzCatDB).

createdupdated
2002-07-012011-02-21


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