DB code: S00295

RLCP classification 1.13.30000.9 : Hydrolysis
CATH domain 3.40.50.200 : Rossmann fold Catalytic domain
E.C. 3.4.21.64
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.200 : Rossmann fold S00296 D00219 S00519

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P06873 Proteinase K
EC 3.4.21.64
Tritirachium alkaline proteinase
Endopeptidase K
S08.054 (Serine)
PF05922 (Inhibitor_I9)
PF00082 (Peptidase_S8)
[Graphical View]

KEGG enzyme name
peptidase K
Tritirachium alkaline proteinase
Tritirachium album serine proteinase
proteinase K
Tritirachium album proteinase K
endopeptidase K

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P06873 PRTK_TRIAL Hydrolysis of keratin, and of other proteins with subtilisin-like specificity. Hydrolyzes peptide amides. Binds 2 calcium ions per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00012 C00001 C00017 C00012 I00087 I00085 I00086
E.C.
Compound Protein Peptide H2O Protein Peptide Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1bjrE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:VAL-ALA-GLN-GLY-GLY-ALA-ALA-GLY-LEU-ALA Unbound Unbound Unbound Unbound Unbound
1egqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ic6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pekE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:PRO-ALA-PRO-PHE (chain C) Bound:ALA-ALA (chain D) Unbound Unbound Unbound
1ptkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2pkcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2prkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3prkE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:MSU-ALA-ALA-PRO-ALA-CH2

Reference for Active-site residues
resource references E.C.
Swiss-prot;P06873 & PDB;1pek, 1ptk

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bjrE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
1egqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
1ic6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
1pekE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
1ptkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
2pkcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
2prkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224
3prkE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 39;HIS 69;ASN 161;THR 223;SER 224 SER 224

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig.8, p.164-168 3

References
[1]
Resource
Comments X-ray crystallography
Medline ID 84261419
PubMed ID 6378621
Journal EMBO J
Year 1984
Volume 3
Pages 1311-4
Authors Paehler A, Banerjee A, Dattagupta JK, Fujiwara T, Lindner K, Pal GP, Suck D, Weber G, Saenger W
Title Three-dimensional structure of fungal proteinase K reveals similarity to bacterial subtilisin.
Related PDB
Related UniProtKB P06873
[2]
Resource
Comments X-ray crystallography (1.5 Angstroms)
Medline ID
PubMed ID 3271105
Journal Acta Crystallogr B
Year 1988
Volume 44
Pages 163-72
Authors Betzel C, Pal GP, Saenger W
Title Synchrotron X-ray data collection and restrained least-squares refinement of the crystal structure of proteinase K at 1.5 A resolution.
Related PDB 2prk
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (1.5 Angstroms)
Medline ID
PubMed ID 3203685
Journal Eur J Biochem
Year 1988
Volume 178
Pages 155-71
Authors Betzel C, Pal GP, Saenger W
Title Three-dimensional structure of proteinase K at 0.15-nm resolution.
Related PDB 1ptk
Related UniProtKB
[4]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID
PubMed ID 1894649
Journal J Biol Chem
Year 1991
Volume 266
Pages 17695-9
Authors Wolf WM, Bajorath J, Muller A, Raghunathan S, Singh TP, Hinrichs W, Saenger W
Title Inhibition of proteinase K by methoxysuccinyl-Ala-Ala-Pro-Ala-chloromethyl ketone. An x-ray study at 2.2-A resolution.
Related PDB 3prkE
Related UniProtKB
[5]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID
PubMed ID 8340410
Journal J Biol Chem
Year 1993
Volume 268
Pages 15854-8
Authors Betzel C, Singh TP, Visanji M, Peters K, Fittkau S, Saenger W, Wilson KS
Title Structure of the complex of proteinase K with a substrate analogue hexapeptide inhibitor at 2.2-A resolution.
Related PDB 1pekE
Related UniProtKB
[6]
Resource
Comments X-ray crystallography (1.5 Angstroms)
Medline ID
PubMed ID 8083213
Journal J Biol Chem
Year 1994
Volume 269
Pages 23108-11
Authors Muller A, Hinrichs W, Wolf WM, Saenger W
Title Crystal structure of calcium-free proteinase K at 1.5-A resolution.
Related PDB 2pkc
Related UniProtKB P06873
[7]
Resource
Comments X-ray crystallography (2.44 Angstroms)
Medline ID 98412873
PubMed ID 9741842
Journal Proteins
Year 1998
Volume 33
Pages 30-8
Authors Singh TP, Sharma S, Karthikeyan S, Betzel C, Bhatia KL
Title Crystal structure of a complex formed between proteolytically-generated lactoferrin fragment and proteinase K.
Related PDB 1bjrE
Related UniProtKB P06873
[8]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID
PubMed ID 10737944
Journal Proteins
Year 2000
Volume 39
Pages 226-34
Authors Gupta MN, Tyagi R, Sharma S, Karthikeyan S, Singh TP
Title Enhancement 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 PDB 1cnm
Related UniProtKB
[9]
Resource
Comments X-ray crystallography (0.98 Angstroms)
Medline ID
PubMed ID 11258922
Journal Biochemistry
Year 2001
Volume 40
Pages 3080-8
Authors Betzel C, Gourinath S, Kumar P, Kaur P, Perbandt M, Eschenburg S, Singh TP
Title Structure of a serine protease proteinase K from Tritirachium album limber at 0.98 A resolution.
Related PDB 1ic6A
Related UniProtKB
[10]
Resource
Comments X-ray crystallography, catalysis
Medline ID
PubMed ID 11563328
Journal Indian J Biochem Biophys
Year 2001
Volume 38
Pages 34-41
Authors Sharma S, Tyagi R, Gupta MN, Singh TP
Title Enhancement of catalytic activity of enzymes by heating in anhydrous organic solvents: 3D structure of a modified serine proteinase at high resolution.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-ray crystallography (1.5 Angstroms)
Medline ID
PubMed ID 11438752
Journal Protein Eng
Year 2001
Volume 14
Pages 307-13
Authors Singh RK, Gourinath S, Sharma S, Roy I, Gupta MN, Betzel C, Srinivasan A, Singh TP
Title Enhancement of enzyme activity through three-phase partitioning: crystal structure of a modified serine proteinase at 1.5 A resolution.
Related PDB 1egq
Related UniProtKB

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).

Created Updated
2002-07-01 2011-02-21