EzCatDB: D00439

DB codeD00439
RLCP classification1.13.200.966
CATH domainDomain 12.40.70.10Catalytic domain
Domain 22.40.70.10Catalytic domain
E.C.3.4.23.20
CSA1apt

CATH domainRelated DB codes (homologues)
2.40.70.10D00471,D00436,D00438,D00440,D00441,D00442,D00443,D00437,D00444,D00423,D00445,D00484,M00206,M00166,D00231,D00529

Enzyme Name
Swiss-protKEGG

P00798
Protein namePenicillopepsinpenicillopepsin
peptidase A
Penicillium janthinellum aspartic proteinase
acid protease A
Penicillium citrinum acid proteinase
Penicillium cyclopium acid proteinase
Penicillium expansum acid proteinase
Penicillium janthinellum acid proteinase
Penicillium expansum aspartic proteinase
Penicillium aspartic proteinase
Penicillium caseicolum aspartic proteinase
Penicillium roqueforti acid proteinase
Penicillium duponti aspartic proteinase
Penicillium citrinum aspartic proteinase
SynonymsEC 3.4.23.20
Peptidase A


Swiss-prot:Accession NumberP00798
Entry namePENP_PENJA
ActivityHydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1'', but also cleaving 20-Gly-|-Glu-21 in the B chain of insulin. Clots milk, and activates trypsinogen.
Subunit
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00012C00017L00076L00078C00001C00012C00017C00298I00136
CompoundPeptideProteinTrypsinogenCaseinH2OPeptideProteinTrypsinAmino-diol-tetrahedral intermediate
Typepeptide/proteinpeptide/proteinpeptide/proteinpeptide/protein,phosphate group/phosphate ionH2Opeptide/proteinpeptide/proteinpeptide/protein
1aptE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:IVA-VAL-VAL-LTA(chain I)
1apuE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:IVA-VAL-VAL-STA(chain I)
1apvE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:IVA-VAL-VAL-DFO-NME(chain I)
1apwE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:IVA-VAL-VAL-DFI-NME(chain I)
1bxoA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP7
1bxqA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP8
1ppkE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:IVV
1pplE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:1Z7
1ppmE01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:0P1
1weaA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP6
1webA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP4
1wecA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP5
1wedA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP6
2weaA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP6
2webA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP4
2wecA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP5
2wedA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundTransition-state-analogue:PP6
3appA01UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1aptE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1apuE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1apvE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1apwE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1bxoA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1bxqA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1ppkE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1pplE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1ppmE02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1weaA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1webA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1wecA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
1wedA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2weaA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2webA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2wecA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
2wedA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound
3appA02UnboundUnboundUnboundUnbound
UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00798
pdbCatalytic residues
1aptE01ASP 33
1apuE01ASP 33
1apvE01ASP 33
1apwE01ASP 33
1bxoA01ASP 33
1bxqA01ASP 33
1ppkE01ASP 33
1pplE01ASP 33
1ppmE01ASP 33
1weaA01ASP 33
1webA01ASP 33
1wecA01ASP 33
1wedA01ASP 33
2weaA01ASP 33
2webA01ASP 33
2wecA01ASP 33
2wedA01ASP 33
3appA01ASP 33
1aptE02ASP 213
1apuE02ASP 213
1apvE02ASP 213
1apwE02ASP 213
1bxoA02ASP 213
1bxqA02ASP 213
1ppkE02ASP 213
1pplE02ASP 213
1ppmE02ASP 213
1weaA02ASP 213
1webA02ASP 213
1wecA02ASP 213
1wedA02ASP 213
2weaA02ASP 213
2webA02ASP 213
2wecA02ASP 213
2wedA02ASP 213
3appA02ASP 213

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]Fig.13, p.3709-3711
[8]Fig.2
[16]Fig.3, p.5207
[17]Fig.10, p.3883-3885

references
[1]
CommentsACTIVE SITE.
Medline ID71018406
PubMed ID5475460
JournalCan J Biochem
Year1970
Volume48
Pages1014-6
AuthorsSodek J, Hofmann T
TitleAmino acid sequence around the active site aspartic acid in penicillopepsin.
Related Swiss-protP00798
[2]
PubMed ID6769571
JournalCan J Biochem
Year1980
Volume58
Pages252-71
AuthorsJames MN
TitleAn X-ray crystallographic approach to enzyme structure and function.
[3]
PubMed ID6755464
JournalProc Natl Acad Sci U S A
Year1982
Volume79
Pages6137-41
AuthorsJames MN, Sielecki A, Salituro F, Rich DH, Hofmann T
TitleConformational flexibility in the active sites of aspartyl proteinases revealed by a pepstatin fragment binding to penicillopepsin.
[4]
CommentsX-ray crystallography
PubMed ID6341600
JournalJ Mol Biol
Year1983
Volume163
Pages299-361
AuthorsJames MN, Sielecki AR
TitleStructure and refinement of penicillopepsin at 1.8 A resolution.
Related PDB3app
[5]
CommentsX-ray crystallography (ISBN: 0935940022)
JournalPeptides: Structure and Function, Proceedings of the of the Eighth American Peptide Symposium
Year1983
Volume1
Pages521-30
AuthorsJames MNG, Sielecki AR, Moult J
TitleCrystallographic Analysis of a Pepstatin Analogue Binding to the Aspartyl Proteinase Penicillopepsin at 1.8 Angstroms Resolution.
Related PDB1apt,1apu
[6]
PubMed ID3912235
JournalBiochem Soc Trans
Year1985
Volume13
Pages1044-6
AuthorsBlum M, Cunningham A, Bendiner M, Hofmann T
TitlePenicillopepsin, the aspartic proteinase from Penicillium janthinellum: substrate-binding effects and intermediates in transpeptidation reactions.
[7]
PubMed ID3899173
JournalBiochemistry
Year1985
Volume24
Pages3701-13
AuthorsJames MN, Sielecki AR
TitleStereochemical analysis of peptide bond hydrolysis catalyzed by the aspartic proteinase penicillopepsin.
[8]
PubMed ID3927973
JournalBiochemistry
Year1985
Volume24
Pages3165-73
AuthorsRich DH, Bernatowicz MS, Agarwal NS, Kawai M, Salituro FG, Schmidt PG
TitleInhibition of aspartic proteases by pepstatin and 3-methylstatine derivatives of pepstatin. Evidence for collected-substrate enzyme inhibition.
[9]
PubMed ID2125469
JournalBiochemistry
Year1990
Volume29
Pages8658-76
AuthorsAvbelj F, Moult J, Kitson DH, James MN, Hagler AT
TitleMolecular dynamics study of the structure and dynamics of a protein molecule in a crystalline ionic environment, Streptomyces griseus protease A.
[10]
PubMed ID2115088
JournalJ Mol Biol
Year1990
Volume214
Pages199-222
AuthorsCooper JB, Khan G, Taylor G, Tickle IJ, Blundell TL
TitleX-ray analyses of aspartic proteinases. II. Three-dimensional structure of the hexagonal crystal form of porcine pepsin at 2.3 A resolution.
[11]
PubMed ID2266566
JournalJ Mol Biol
Year1990
Volume216
Pages991-1016
AuthorsSummers NL, Karplus M
TitleModeling of globular proteins. A distance-based data search procedure for the construction of insertion/deletion regions and Pro----non-Pro mutations.
[12]
PubMed ID2217165
JournalProteins
Year1990
Volume8
Pages62-81
AuthorsAbad-Zapatero C, Rydel TJ, Erickson J
TitleRevised 2.3 A structure of porcine pepsin: evidence for a flexible subdomain.
[13]
PubMed ID1812712
JournalAdv Exp Med Biol
Year1991
Volume306
Pages243-54
AuthorsHofmann T, Blum M, Cunningham A
TitleStudies on the mechanism of action of penicillopepsin.
[14]
PubMed ID2033049
JournalJ Biol Chem
Year1991
Volume266
Pages9501-7
AuthorsBlum M, Cunningham A, Pang H, Hofmann T
TitleMechanism and pathway of penicillopepsin-catalyzed transpeptidation and evidence for noncovalent trapping of amino acid and peptide intermediates.
[15]
PubMed ID2056534
JournalJ Mol Biol
Year1991
Volume219
Pages671-92
AuthorsSielecki AR, Fujinaga M, Read RJ, James MN
TitleRefined structure of porcine pepsinogen at 1.8 A resolution.
[16]
CommentsX-ray crystallography
PubMed ID1606144
JournalBiochemistry
Year1992
Volume31
Pages5201-14
AuthorsFraser ME, Strynadka NC, Bartlett PA, Hanson JE, James MN
TitleCrystallographic analysis of transition-state mimics bound to penicillopepsin: phosphorus-containing peptide analogues.
Related PDB1ppk,1ppl,1ppm
[17]
CommentsX-ray crystallography
PubMed ID1567842
JournalBiochemistry
Year1992
Volume31
Pages3872-86
AuthorsJames MN, Sielecki AR, Hayakawa K, Gelb MH
TitleCrystallographic analysis of transition state mimics bound to penicillopepsin: difluorostatine- and difluorostatone-containing peptides.
Related PDB1apv,1apw
[18]
PubMed ID8345528
JournalJ Mol Biol
Year1993
Volume232
Pages701-3
AuthorsBadasso M, Wood SP, Aguilar C, Cooper JB, Blundell TL, Dreyer T
TitleCrystallization and preliminary crystallographic characterization of aspartic proteinase-A from baker's yeast and its complexes with inhibitors.
[19]
PubMed ID7932732
JournalJ Mol Biol
Year1994
Volume243
Pages100-15
AuthorsJiang JS, Brunger AT
TitleProtein hydration observed by X-ray diffraction. Solvation properties of penicillopepsin and neuraminidase crystal structures.
[20]
PubMed ID9379922
JournalMethods Enzymol
Year1997
Volume277
Pages131-57
AuthorsFortier S, Chiverton A, Glasgow J, Leherte L
TitleCritical-point analysis in protein electron-density map interpretation.
[21]
CommentsX-ray crystallography
PubMed ID9561242
JournalAdv Exp Med Biol
Year1998
Volume436
Pages355-9
AuthorsFraser ME, Meyer JH, Bartlett PA, James MN
TitleOvercoming the unfavourable entropic contribution of ligand binding with a macrocyclic inhibitor bound to penicillopepsin.
Related PDB1wea,1web,1wec,1wed,2wea,2web,2wec,2wed
[22]
CommentsX-RAY CRYSTALLOGRAPHY (0.95 ANGSTROMS).
Medline ID99055159
PubMed ID9836576
JournalBiochemistry
Year1998
Volume37
Pages16839-45
AuthorsKhan AR, Parrish JC, Fraser ME, Smith WW, Bartlett PA, James MN
TitleLowering the entropic barrier for binding conformationally flexible inhibitors to enzymes.
Related PDB1bxo,1bxq
Related Swiss-protP00798
[23]
PubMed ID10850809
JournalProtein Sci
Year2000
Volume9
Pages991-1001
AuthorsCao QN, Stubbs M, Ngo KQ, Ward M, Cunningham A, Pai EF, Tu GC, Hofmann T
TitlePenicillopepsin-JT2, a recombinant enzyme from Penicillium janthinellum and the contribution of a hydrogen bond in subsite S3 to k(cat).
[24]
PubMed ID12036355
JournalJ Med Chem
Year2002
Volume45
Pages2469-83
AuthorsCozzini P, Fornabaio M, Marabotti A, Abraham DJ, Kellogg GE, Mozzarelli A
TitleSimple, intuitive calculations of free energy of binding for protein-ligand complexes. 1. Models without explicit constrained water.

comments
This enzyme belongs to the peptidase family-A1.
This enzyme has got a catalytic dyad, composed of two aspartic acid residues, which is observed in other aspartate proteases, such as pepsin (D00436 in EzCatDB). It suggests that it may have a similar reaction mechanism.

createdupdated
2004-10-272012-06-27


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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