DB code: D00436

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. 3.4.23.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1 D00471 D00438 D00439 D00440 D00441 D00442 D00443 D00437 D00444 D00423 D00445 D00484 M00206 M00166 D00231 D00529

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam RefSeq
P00791 Pepsin A
EC 3.4.23.1
A01.001 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]
P0DJD9
None A01.071 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]
NP_055039.1 (Protein)
NM_014224.2 (DNA/RNA sequence)

KEGG enzyme name
pepsin A
pepsin
lactated pepsin
pepsin fortior
fundus-pepsin
elixir lactate of pepsin
P I
lactated pepsin elixir
P II
pepsin R
pepsin D

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00791 PEPA_PIG Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1'' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the B chain of insulin. Secreted.
P0DJD9 PEPA5_HUMAN Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the B chain of insulin. Secreted.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00017 C00001 C00012 C00017 I00136
E.C.
Compound Peptide Protein H2O Peptide Protein Amino-diol-tetrahedral intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1f34A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1psaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:0ZL Unbound Unbound Unbound Unbound
1psaB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:0ZL Unbound Unbound Unbound Unbound
1yx9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2psgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3pepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3psgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
4pepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
5pepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1flhA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1psnA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1psoE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:IVA-VAL-VAL-STA-ALA-STA(chain I) Unbound Unbound Unbound Unbound
1qrpE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Transition-state-analogue:HH0
3utlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1f34A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:GLN_1(chain B) Unbound
1psaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1psaB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1yx9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2psgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3pepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3psgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
4pepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
5pepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1flhA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1psnA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1psoE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qrpE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3utlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1f34A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1psaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1psaB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1yx9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
2psgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
3pepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
3psgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
4pepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
5pepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1flhA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1psnA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1psoE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1qrpE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
3utlA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 32
1f34A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1psaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1psaB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1yx9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
2psgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
3pepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
3psgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
4pepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
5pepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1flhA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1psnA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1psoE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
1qrpE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215
3utlA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 215

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
Fig.5, p.7010-7012 3
[23]
p.18414-18417
[25]
Fig.5, p.3331-3332 3
[41]
p.276-278
[46]
Fig.6

References
[1]
Resource
Comments ACTIVE SITE.
Medline ID 69283592
PubMed ID 4897201
Journal Biochem J
Year 1969
Volume 113
Pages 377-86
Authors Bayliss RS, Knowles JR, Wybrandt GB
Title An aspartic acid residue at the active site of pepsin. The isolation and sequence of the heptapeptide.
Related PDB
Related UniProtKB P00791
[2]
Resource
Comments
Medline ID
PubMed ID 4940603
Journal Arch Biochem Biophys
Year 1971
Volume 144
Pages 59-65
Authors Nakagawa Y, Perlmann GE
Title Disulfide bonds of pepsinogen and pepsin: identification of the disulfide bonds which can be reversibly reduced and reoxidized.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 4946266
Journal Biochem Biophys Res Commun
Year 1971
Volume 45
Pages 293-6
Authors Hubbard CD, Stein TP
Title The pepsin catalysed hydrolysis of bis-P-nitrophenyl sulfite.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 4561920
Journal Biochem J
Year 1972
Volume 127
Pages 35P
Authors Takahashi M, Hofmann T
Title Evidence for an acyl intermediate in pepsin-catalysed reactions.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 782445
Journal Biochem J
Year 1976
Volume 153
Pages 691-9
Authors Wang TT, Hofmann T
Title Acyl and amino intermediates in reactions catalysed by pig pepsin. Analysis of transpeptidation products.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY.
Medline ID 78077917
PubMed ID 339692
Journal Adv Exp Med Biol
Year 1977
Volume 95
Pages 23-31
Authors Andreeva NS, Gustchina AE, Fedorov AA, Shutzkever NE, Volnova TV
Title X-ray crystallographic studies of pepsin.
Related PDB
Related UniProtKB P00791
[7]
Resource
Comments
Medline ID
PubMed ID 346376
Journal FEBS Lett
Year 1978
Volume 88
Pages 87-90
Authors Antonov VK, Ginodman LM, Kapitannikov YV, Barshevskaya TN, Gurova AG, Rumsh LD
Title Mechanism of pepsin catalysis: general base catalysis by the active-site carboxylate ion.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 2862261
Journal J Pharm Pharmacol
Year 1985
Volume 37
Pages 396-400
Authors Lawton JB, Mekas CI
Title The effect of polycations on the activity of pepsin.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 3109484
Journal Biochim Biophys Acta
Year 1987
Volume 913
Pages 122-30
Authors Dunn BM, Valler MJ, Rolph CE, Foundling SI, Jimenez M, Kay J
Title The pH dependence of the hydrolysis of chromogenic substrates of the type, Lys-Pro-Xaa-Yaa-Phe-(NO2)Phe-Arg-Leu, by selected aspartic proteinases: evidence for specific interactions in subsites S3 and S2.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 3313384
Journal Proc Natl Acad Sci U S A
Year 1987
Volume 84
Pages 7009-13
Authors Suguna K, Padlan EA, Smith CW, Carlson WD, Davies DR
Title Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2492190
Journal Biochem Biophys Res Commun
Year 1989
Volume 158
Pages 115-9
Authors McPhie P
Title A reversible unfolding reaction of swine pepsin; implications for pepsinogen's folding mechanism.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 90317821
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 5pep
Related UniProtKB P00791
[13]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 2115087
Journal J Mol Biol
Year 1990
Volume 214
Pages 143-70
Authors Sielecki AR, Fedorov AA, Boodhoo A, Andreeva NS, James MN
Title Molecular and crystal structures of monoclinic porcine pepsin refined at 1.8 A resolution.
Related PDB 4pep
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 91017500
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 3pep
Related UniProtKB P00791
[15]
Resource
Comments
Medline ID
PubMed ID 1812734
Journal Adv Exp Med Biol
Year 1991
Volume 306
Pages 39-45
Authors Andreeva NS, James MN
Title Why does pepsin have a negative charge at very low pH? An analysis of conserved charged residues in aspartic proteinases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 2065096
Journal Biochim Biophys Acta
Year 1991
Volume 1078
Pages 283-8
Authors Makarov AA, Protasevich II, Frank EG, Grishina IB, Bolotina IA, Esipova NG
Title The number of cooperative regions (energetic domains) in a pepsin molecule depends on the pH of the medium.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 1820069
Journal Biomed Biochim Acta
Year 1991
Volume 50
Pages S94-7
Authors Bemquerer MP, Theobaldo FC, Tominaga M
Title Pepsin-catalyzed peptide synthesis in biphasic systems.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 1820070
Journal Biomed Biochim Acta
Year 1991
Volume 50
Pages S98-101
Authors Filippova IYu, Lysogorskaya EN, Anisimova VV, Abdel Malak CA, Lavrenova GI, Stepanov VM
Title Pepsin behavior as a catalyst in equilibrium-controlled peptide synthesis.
Related PDB
Related UniProtKB
[19]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 91278095
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 2psg
Related UniProtKB P00791
[20]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 1418819
Journal Acta Crystallogr B
Year 1992
Volume 48
Pages 476-88
Authors Chen L, Erickson JW, Rydel TJ, Park CH, Neidhart D, Luly J, Abad-Zapatero C
Title Structure of a pepsin/renin inhibitor complex reveals a novel crystal packing induced by minor chemical alterations in the inhibitor.
Related PDB 1psa
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 1428533
Journal Int J Pept Protein Res
Year 1992
Volume 39
Pages 443-9
Authors Abdel Malak C, Filippova IY, Lysogorskaya EN, Anisimova VV, Lavrenova GI, Stepanov VM
Title Pepsin as a catalyst of peptide synthesis. Enzyme co-precipitation with emerging peptide products.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 1512263
Journal J Biol Chem
Year 1992
Volume 267
Pages 17257-63
Authors Lin XL, Lin YZ, Koelsch G, Gustchina A, Wlodawer A, Tang J
Title Enzymic activities of two-chain pepsinogen, two-chain pepsin, and the amino-terminal lobe of pepsinogen.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 1526982
Journal J Biol Chem
Year 1992
Volume 267
Pages 18413-8
Authors Lin Y, Fusek M, Lin X, Hartsuck JA, Kezdy FJ, Tang J
Title pH dependence of kinetic parameters of pepsin, rhizopuspepsin, and their active-site hydrogen bond mutants.
Related PDB
Related UniProtKB
[24]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID 92279205
PubMed ID 1594574
Journal Proteins
Year 1992
Volume 13
Pages 1-25
Authors Hartsuck JA, Koelsch G, Remington SJ
Title The high-resolution crystal structure of porcine pepsinogen.
Related PDB 3psg
Related UniProtKB P00791
[25]
Resource
Comments
Medline ID
PubMed ID 8461297
Journal Biochemistry
Year 1993
Volume 32
Pages 3325-33
Authors Beveridge AJ, Heywood GC
Title A quantum mechanical study of the active site of aspartic proteinases.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 8401224
Journal Protein Sci
Year 1993
Volume 2
Pages 1383-90
Authors Lin X, Loy JA, Sussman F, Tang J
Title Conformational instability of the N- and C-terminal lobes of porcine pepsin in neutral and alkaline solutions.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 7925992
Journal FEBS Lett
Year 1994
Volume 352
Pages 315-7
Authors Iliadis G, Zundel G, Brzezinski B
Title Aspartic proteinases--Fourier transform IR studies of the aspartic carboxylic groups in the active site of pepsin.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 8138045
Journal Int J Biochem
Year 1994
Volume 26
Pages 35-42
Authors Balbaa M, Blum M, Hofmann T
Title Mechanism of pepsin-catalyzed aminotranspeptidation reactions.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 7896503
Journal Int J Pept Protein Res
Year 1994
Volume 44
Pages 448-56
Authors Bemquerer MP, Adlercreutz P, Tominaga M
Title Pepsin-catalyzed peptide synthesis in organic media: studies with free and immobilized enzyme.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 8540318
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 19-32
Authors Andreeva NS, Bochkarev A, Pechik I
Title A new way of looking at aspartic proteinase structures: a comparison of pepsin structure to other aspartic proteinases in the near active site region.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 8540385
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 91-4
Authors Rao C, Dunn BM
Title Evidence for electrostatic interactions in the S2 subsite of porcine pepsin.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 8556555
Journal Clin Exp Allergy
Year 1995
Volume 25
Pages 1007-17
Authors Schmidt DG, Meijer RJ, Slangen CJ, van Beresteijn EC
Title Raising the pH of the pepsin-catalysed hydrolysis of bovine whey proteins increases the antigenicity of the hydrolysates.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 7650014
Journal J Biol Chem
Year 1995
Volume 270
Pages 19974-8
Authors Cottrell TJ, Harris LJ, Tanaka T, Yada RY
Title The sole lysine residue in porcine pepsin works as a key residue for catalysis and conformational flexibility.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 7593830
Journal J Dairy Res
Year 1995
Volume 62
Pages 451-67
Authors Plowman JE, Creamer LK
Title Restrained molecular dynamics study of the interaction between bovine kappa-casein peptide 98-111 and bovine chymosin and porcine pepsin.
Related PDB
Related UniProtKB
[35]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 95392399
PubMed ID 7663352
Journal Protein Sci
Year 1995
Volume 4
Pages 960-72
Authors Fujinaga M, Chernaia MM, Tarasova NI, Mosimann SC, James MN
Title Crystal structure of human pepsin and its complex with pepstatin.
Related PDB 1psn 1pso
Related UniProtKB P00790
[36]
Resource
Comments
Medline ID
PubMed ID 8907496
Journal Int J Pept Protein Res
Year 1996
Volume 47
Pages 28-35
Authors Anisimova VV, Filippova IY, Lysogorskaya EN, Oksenoit ES, Kolobanova SV, Stepanov VM
Title Proteinase-catalyzed peptide synthesis in concentrated solutions of urea and other denaturing agents.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 9228062
Journal J Biol Chem
Year 1997
Volume 272
Pages 18855-61
Authors Shintani T, Nomura K, Ichishima E
Title Engineering of porcine pepsin. Alteration of S1 substrate specificity of pepsin to those of fungal aspartic proteinases by site-directed mutagenesis.
Related PDB
Related UniProtKB
[38]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9761815
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 32-46
Authors Karlsen S, Hough E, Olsen RL
Title Structure and proposed amino-acid sequence of a pepsin from atlantic cod (Gadus morhua).
Related PDB 1am5
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 10408333
Journal J Pept Res
Year 1999
Volume 53
Pages 606-10
Authors Malak CA
Title Pepsin as a catalyst for peptide synthesis: formation of peptide bonds not typical for pepsin substrate specificity.
Related PDB
Related UniProtKB
[40]
Resource
Comments
Medline ID
PubMed ID 10065711
Journal Protein Eng
Year 1999
Volume 12
Pages 55-61
Authors Okoniewska M, Tanaka T, Yada RY
Title The role of the flap residue, threonine 77, in the activation and catalytic activity of pepsin A.
Related PDB
Related UniProtKB
[41]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10713513
Journal Acta Crystallogr D Biol Crystallogr
Year 2000
Volume 56
Pages 272-9
Authors Fujinaga M, Cherney MM, Tarasova NI, Bartlett PA, Hanson JE, James MN
Title Structural study of the complex between human pepsin and a phosphorus-containing peptidic -transition-state analog.
Related PDB 1qrp
Related UniProtKB
[42]
Resource
Comments
Medline ID
PubMed ID 10861225
Journal Biochem J
Year 2000
Volume 349
Pages 169-77
Authors Okoniewska M, Tanaka T, Yada RY
Title The pepsin residue glycine-76 contributes to active-site loop flexibility and participates in catalysis.
Related PDB
Related UniProtKB
[43]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10932249
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 653-7
Authors Ng KK, Petersen JF, Cherney MM, Garen C, Zalatoris JJ, Rao-Naik C, Dunn BM, Martzen MR, Peanasky RJ, James MN
Title Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3.
Related PDB 1f34
Related UniProtKB
[44]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11679720
Journal Acta Crystallogr D Biol Crystallogr
Year 2001
Volume 57
Pages 1560-70
Authors Canduri F, Teodoro LG, Fadel V, Lorenzi CC, Hial V, Gomes RA, Neto JR, de Azevedo WF Jr
Title Structure of human uropepsin at 2.45 A resolution.
Related PDB 1flh
Related UniProtKB
[45]
Resource
Comments
Medline ID
PubMed ID 11707613
Journal Protein Eng
Year 2001
Volume 14
Pages 669-74
Authors Tanaka T, Yada RY
Title N-terminal portion acts as an initiator of the inactivation of pepsin at neutral pH.
Related PDB
Related UniProtKB
[46]
Resource
Comments
Medline ID
PubMed ID 11714911
Journal Protein Sci
Year 2001
Volume 10
Pages 2439-50
Authors Andreeva NS, Rumsh LD
Title Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes.
Related PDB
Related UniProtKB
[47]
Resource
Comments
Medline ID
PubMed ID 12089768
Journal Q Rev Biol
Year 2002
Volume 77
Pages 127-47
Authors Fruton JS
Title A history of pepsin and related enzymes.
Related PDB
Related UniProtKB
[48]
Resource
Comments
Medline ID
PubMed ID 15883044
Journal Biochem Biophys Res Commun
Year 2005
Volume 331
Pages 1510-4
Authors Kesavulu MM, Ramasubramanian S, Suguna K
Title Effect of dimethyl sulphoxide on the crystal structure of porcine pepsin.
Related PDB 1yx9
Related UniProtKB
[49]
Resource
Comments
Medline ID
PubMed ID 22525752
Journal Acta Crystallogr D Biol Crystallogr
Year 2012
Volume 68
Pages 541-52
Authors Bailey D, Carpenter EP, Coker A, Coker S, Read J, Jones AT, Erskine P, Aguilar CF, Badasso M, Toldo L, Rippmann F, Sanz-Aparicio J, Albert A, Blundell TL, Roberts NB, Wood SP, Cooper JB
Title An analysis of subdomain orientation, conformational change and disorder in relation to crystal packing of aspartic proteinases.
Related PDB 3utl
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-A1.
According to the literature [10], [25] & [41], the catalytic reaction proceeds as follows:
(1) Asp215 acts as a general base, abstracting a proton from a water molecule, which is bound between Asp32 and Asp215.
(2) The activated water, or the nucleophilic hydroxide ion, makes an attack on the carbonyl carbon atom of the substrate peptide bond, leading to the formation of a tetrahedral transition state with a negatively charged oxyanion (or gem-diol).
(3) The protonated carboxyl sidechain of Asp32 stabilzes the negative charge of the transition state.
(4) Asp215 acts as a general acid, protonating to the leaving amine group. This step leads to the cleavage of the peptide bond.

Created Updated
2004-10-14 2012-06-27