DB code: D00439

RLCP classification 1.13.200.966 : Hydrolysis
CATH domain 2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
E.C. 3.4.23.20
CSA 1apt
M-CSA 1apt
MACiE

CATH domain Related DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1 D00471 D00436 D00438 D00440 D00441 D00442 D00443 D00437 D00444 D00423 D00445 D00484 M00206 M00166 D00231 D00529

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P00798 Penicillopepsin
EC 3.4.23.20
Peptidase A
A01.011 (Aspartic)
PF00026 (Asp)
[Graphical View]

KEGG enzyme name
penicillopepsin
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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00798 PENP_PENJA Hydrolysis 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.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00017 L00076 L00078 C00001 C00012 C00017 C00298 I00136
E.C.
Compound Peptide Protein Trypsinogen Casein H2O Peptide Protein Trypsin Amino-diol-tetrahedral intermediate
Type peptide/protein peptide/protein peptide/protein peptide/protein,phosphate group/phosphate ion H2O peptide/protein peptide/protein peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1aptE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:IVA-VAL-VAL-LTA (chain I)
1apuE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:IVA-VAL-VAL-STA (chain I)
1apvE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:IVA-VAL-VAL-DFO-NME (chain I)
1apwE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:IVA-VAL-VAL-DFI-NME (chain I)
1bxoA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP7
1bxqA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP8
1ppkE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:IVV
1pplE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:1Z7
1ppmE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:0P1
1weaA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP6
1webA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP4
1wecA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP5
1wedA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP6
2weaA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP6
2webA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP4
2wecA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP5
2wedA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:PP6
3appA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1aptE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1apuE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1apvE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1apwE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bxoA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1bxqA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ppkE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1pplE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ppmE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1weaA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1webA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1wecA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1wedA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2weaA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2webA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2wecA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2wedA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3appA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00798

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1aptE01 ASP 33
1apuE01 ASP 33
1apvE01 ASP 33
1apwE01 ASP 33
1bxoA01 ASP 33
1bxqA01 ASP 33
1ppkE01 ASP 33
1pplE01 ASP 33
1ppmE01 ASP 33
1weaA01 ASP 33
1webA01 ASP 33
1wecA01 ASP 33
1wedA01 ASP 33
2weaA01 ASP 33
2webA01 ASP 33
2wecA01 ASP 33
2wedA01 ASP 33
3appA01 ASP 33
1aptE02 ASP 213
1apuE02 ASP 213
1apvE02 ASP 213
1apwE02 ASP 213
1bxoA02 ASP 213
1bxqA02 ASP 213
1ppkE02 ASP 213
1pplE02 ASP 213
1ppmE02 ASP 213
1weaA02 ASP 213
1webA02 ASP 213
1wecA02 ASP 213
1wedA02 ASP 213
2weaA02 ASP 213
2webA02 ASP 213
2wecA02 ASP 213
2wedA02 ASP 213
3appA02 ASP 213

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments ACTIVE SITE.
Medline ID 71018406
PubMed ID 5475460
Journal Can J Biochem
Year 1970
Volume 48
Pages 1014-6
Authors Sodek J, Hofmann T
Title Amino acid sequence around the active site aspartic acid in penicillopepsin.
Related PDB
Related UniProtKB P00798
[2]
Resource
Comments
Medline ID
PubMed ID 6769571
Journal Can J Biochem
Year 1980
Volume 58
Pages 252-71
Authors James MN
Title An X-ray crystallographic approach to enzyme structure and function.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 6755464
Journal Proc Natl Acad Sci U S A
Year 1982
Volume 79
Pages 6137-41
Authors James MN, Sielecki A, Salituro F, Rich DH, Hofmann T
Title Conformational flexibility in the active sites of aspartyl proteinases revealed by a pepstatin fragment binding to penicillopepsin.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 6341600
Journal J Mol Biol
Year 1983
Volume 163
Pages 299-361
Authors James MN, Sielecki AR
Title Structure and refinement of penicillopepsin at 1.8 A resolution.
Related PDB 3app
Related UniProtKB
[5]
Resource
Comments X-ray crystallography (ISBN: 0935940022)
Medline ID
PubMed ID
Journal Peptides: Structure and Function, Proceedings of the of the Eighth American Peptide Symposium
Year 1983
Volume 1
Pages 521-30
Authors James MNG, Sielecki AR, Moult J
Title Crystallographic Analysis of a Pepstatin Analogue Binding to the Aspartyl Proteinase Penicillopepsin at 1.8 Angstroms Resolution.
Related PDB 1apt 1apu
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 3912235
Journal Biochem Soc Trans
Year 1985
Volume 13
Pages 1044-6
Authors Blum M, Cunningham A, Bendiner M, Hofmann T
Title Penicillopepsin, the aspartic proteinase from Penicillium janthinellum: substrate-binding effects and intermediates in transpeptidation reactions.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 3899173
Journal Biochemistry
Year 1985
Volume 24
Pages 3701-13
Authors James MN, Sielecki AR
Title Stereochemical analysis of peptide bond hydrolysis catalyzed by the aspartic proteinase penicillopepsin.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 3927973
Journal Biochemistry
Year 1985
Volume 24
Pages 3165-73
Authors Rich DH, Bernatowicz MS, Agarwal NS, Kawai M, Salituro FG, Schmidt PG
Title Inhibition of aspartic proteases by pepstatin and 3-methylstatine derivatives of pepstatin. Evidence for collected-substrate enzyme inhibition.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 2125469
Journal Biochemistry
Year 1990
Volume 29
Pages 8658-76
Authors Avbelj F, Moult J, Kitson DH, James MN, Hagler AT
Title Molecular dynamics study of the structure and dynamics of a protein molecule in a crystalline ionic environment, Streptomyces griseus protease A.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 2115088
Journal J Mol Biol
Year 1990
Volume 214
Pages 199-222
Authors Cooper JB, Khan G, Taylor G, Tickle IJ, Blundell TL
Title X-ray analyses of aspartic proteinases. II. Three-dimensional structure of the hexagonal crystal form of porcine pepsin at 2.3 A resolution.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2266566
Journal J Mol Biol
Year 1990
Volume 216
Pages 991-1016
Authors Summers NL, Karplus M
Title Modeling of globular proteins. A distance-based data search procedure for the construction of insertion/deletion regions and Pro----non-Pro mutations.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 2217165
Journal Proteins
Year 1990
Volume 8
Pages 62-81
Authors Abad-Zapatero C, Rydel TJ, Erickson J
Title Revised 2.3 A structure of porcine pepsin: evidence for a flexible subdomain.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 1812712
Journal Adv Exp Med Biol
Year 1991
Volume 306
Pages 243-54
Authors Hofmann T, Blum M, Cunningham A
Title Studies on the mechanism of action of penicillopepsin.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 2033049
Journal J Biol Chem
Year 1991
Volume 266
Pages 9501-7
Authors Blum M, Cunningham A, Pang H, Hofmann T
Title Mechanism and pathway of penicillopepsin-catalyzed transpeptidation and evidence for noncovalent trapping of amino acid and peptide intermediates.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 2056534
Journal J Mol Biol
Year 1991
Volume 219
Pages 671-92
Authors Sielecki AR, Fujinaga M, Read RJ, James MN
Title Refined structure of porcine pepsinogen at 1.8 A resolution.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 1606144
Journal Biochemistry
Year 1992
Volume 31
Pages 5201-14
Authors Fraser ME, Strynadka NC, Bartlett PA, Hanson JE, James MN
Title Crystallographic analysis of transition-state mimics bound to penicillopepsin: phosphorus-containing peptide analogues.
Related PDB 1ppk 1ppl 1ppm
Related UniProtKB
[17]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 1567842
Journal Biochemistry
Year 1992
Volume 31
Pages 3872-86
Authors James MN, Sielecki AR, Hayakawa K, Gelb MH
Title Crystallographic analysis of transition state mimics bound to penicillopepsin: difluorostatine- and difluorostatone-containing peptides.
Related PDB 1apv 1apw
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 8345528
Journal J Mol Biol
Year 1993
Volume 232
Pages 701-3
Authors Badasso M, Wood SP, Aguilar C, Cooper JB, Blundell TL, Dreyer T
Title Crystallization and preliminary crystallographic characterization of aspartic proteinase-A from baker's yeast and its complexes with inhibitors.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 7932732
Journal J Mol Biol
Year 1994
Volume 243
Pages 100-15
Authors Jiang JS, Brunger AT
Title Protein hydration observed by X-ray diffraction. Solvation properties of penicillopepsin and neuraminidase crystal structures.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9379922
Journal Methods Enzymol
Year 1997
Volume 277
Pages 131-57
Authors Fortier S, Chiverton A, Glasgow J, Leherte L
Title Critical-point analysis in protein electron-density map interpretation.
Related PDB
Related UniProtKB
[21]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9561242
Journal Adv Exp Med Biol
Year 1998
Volume 436
Pages 355-9
Authors Fraser ME, Meyer JH, Bartlett PA, James MN
Title Overcoming the unfavourable entropic contribution of ligand binding with a macrocyclic inhibitor bound to penicillopepsin.
Related PDB 1wea 1web 1wec 1wed 2wea 2web 2wec 2wed
Related UniProtKB
[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (0.95 ANGSTROMS).
Medline ID 99055159
PubMed ID 9836576
Journal Biochemistry
Year 1998
Volume 37
Pages 16839-45
Authors Khan AR, Parrish JC, Fraser ME, Smith WW, Bartlett PA, James MN
Title Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes.
Related PDB 1bxo 1bxq
Related UniProtKB P00798
[23]
Resource
Comments
Medline ID
PubMed ID 10850809
Journal Protein Sci
Year 2000
Volume 9
Pages 991-1001
Authors Cao QN, Stubbs M, Ngo KQ, Ward M, Cunningham A, Pai EF, Tu GC, Hofmann T
Title Penicillopepsin-JT2, a recombinant enzyme from Penicillium janthinellum and the contribution of a hydrogen bond in subsite S3 to k(cat).
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12036355
Journal J Med Chem
Year 2002
Volume 45
Pages 2469-83
Authors Cozzini P, Fornabaio M, Marabotti A, Abraham DJ, Kellogg GE, Mozzarelli A
Title Simple, intuitive calculations of free energy of binding for protein-ligand complexes. 1. Models without explicit constrained water.
Related PDB
Related UniProtKB

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.

Created Updated
2004-10-27 2012-06-27