EzCatDB: D00442
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DB codeD00442
RLCP classification1.13.200.966 : Hydrolysis
CATH domainDomain 12.40.70.10 : Cathepsin D, subunit A; domain 1Catalytic domain
Domain 22.40.70.10 : Cathepsin D, subunit A; domain 1Catalytic domain
E.C.3.4.23.23
CSA1mpp

CATH domainRelated DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1D00471,D00436,D00438,D00439,D00440,D00441,D00443,D00437,D00444,D00423,D00445,D00484,M00206,M00166,D00231,D00529

Enzyme Name
UniProtKBKEGG

P00799P09177
Protein nameMucorpepsinMucorpepsinmucorpepsin
Mucor rennin
Mucor aspartic proteinase
Mucor acid proteinase
Mucor acid protease
Mucor miehei aspartic proteinase
Mucor miehei aspartic protease
Mucor aspartic proteinase
Mucor pusillus emporase
Fromase 100
Mucor pusillus rennin
Fromase 46TL
Mucor miehei rennin
SynonymsEC 3.4.23.23
Mucor rennin
EC 3.4.23.23
Mucor rennin
MEROPSA01.013 (Aspartic)
A01.013 (Aspartic)
PfamPF00026 (Asp)
[Graphical view]
PF00026 (Asp)
[Graphical view]


UniProtKB:Accession NumberP00799P09177
Entry nameCARP_RHIMICARP_RHIPU
ActivityHydrolysis of proteins, favoring hydrophobic residues at P1 and P1''. Clots milk. Does not accept Lys at P1, and hence does not activate trypsinogen.Hydrolysis of proteins, favoring hydrophobic residues at P1 and P1''. Clots milk. Does not accept Lys at P1, and hence does not activate trypsinogen.
Subunit

Subcellular location

Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00012L00078C00001C00017C00012I00136
CompoundProteinPeptideCaseinH2OProteinPeptideAmino-diol-tetrahedral intermediate
Typepeptide/proteinpeptide/proteinpeptide/protein,phosphate group/phosphate ionH2Opeptide/proteinpeptide/protein
ChEBI


15377



PubChem


962
22247451



               
1mppA01UnboundUnboundUnbound UnboundUnboundUnbound
2asiA01UnboundUnboundUnbound UnboundUnboundUnbound
2rmpA01Analogue:IVA-VAL-VAL-STA-ALA-STA(chain B)UnboundUnbound UnboundUnboundUnbound
1mppA02UnboundUnboundUnbound UnboundUnboundUnbound
2asiA02UnboundUnboundUnboundBound:HOH 421UnboundUnboundUnbound
2rmpA02UnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
PDB;1e5o,1e80,1e81,1e82,1mpp,2asi & Swiss-prot;P00799,P09177
pdbCatalytic residues
         
1mppA01ASP 32
2asiA01ASP 38
2rmpA01ASP 38
1mppA02ASP 215
2asiA02ASP 237
2rmpA02ASP 237

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.5, p.7010-70123
[12]p.453-456

references
[1]
PubMed ID1125813
JournalCan J Biochem
Year1975
Volume53
Pages269-74
AuthorsRickert WS, McBride-Warren PA
TitleAcid proteases from species of Mucormii. partial characterization of the acid protease produced by a strain of Mucor miehei isolated in Cuba.
[2]
PubMed ID6749830
JournalJ Biochem (Tokyo)
Year1982
Volume91
Pages2039-46
AuthorsEtoh Y, Shoun H, Ogino T, Fujiwara S, Arima K, Beppu T
TitleProton magnetic resonance spectroscopy of an essential histidyl residue in a milk-clotting acid protease, Mucor rennin.
[3]
PubMed ID3313384
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages7009-13
AuthorsSuguna K, Padlan EA, Smith CW, Carlson WD, Davies DR
TitleBinding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
[4]
PubMed ID1963762
JournalAnn N Y Acad Sci
Year1990
Volume613
Pages14-25
AuthorsBeppu T
TitleModification of milk-clotting aspartic proteinases by recombinant DNA techniques.
[5]
PubMed ID2116411
JournalJ Biol Chem
Year1990
Volume265
Pages13955-9
AuthorsAikawa J, Yamashita T, Nishiyama M, Horinouchi S, Beppu T
TitleEffects of glycosylation on the secretion and enzyme activity of Mucor rennin, an aspartic proteinase of Mucor pusillus, produced by recombinant yeast.
[6]
PubMed ID1892395
JournalAppl Environ Microbiol
Year1991
Volume57
Pages2052-6
AuthorsHiramatsu R, Horinouchi S, Uchida E, Hayakawa T, Beppu T
TitleThe secretion leader of Mucor pusillus rennin which possesses an artificial Lys-Arg sequence directs the secretion of mature human growth hormone by Saccharomyces cerevisiae.
[7]
PubMed ID2001389
JournalBiochim Biophys Acta
Year1991
Volume1076
Pages406-15
AuthorsBrown ED, Yada RY
TitleA kinetic and equilibrium study of the denaturation of aspartic proteinases from the fungi, Endothia parasitica and Mucor miehei.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID93195933
PubMed ID8450540
JournalJ Mol Biol
Year1993
Volume230
Pages260-83
AuthorsNewman M, Watson F, Roychowdhury P, Jones H, Badasso M, Cleasby A, Wood SP, Tickle IJ, Blundell TL
TitleX-ray analyses of aspartic proteinases. V. Structure and refinement at 2.0 A resolution of the aspartic proteinase from Mucor pusillus.
Related PDB1mpp
Related UniProtKBP09177
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
JournalActa Crystallogr D Biol Crystallogr
Year1995
Volume51
Pages243-4
AuthorsJia Z, Vandonselaar M, Schneider P, Quail JW
TitleCrystallization and preliminary X-ray structure solution of Rhizomucor miehei aspartic proteinase
Related UniProtKBP00799
[10]
PubMed ID8540364
JournalAdv Exp Med Biol
Year1995
Volume362
Pages501-9
AuthorsBeppu T, Park YN, Aikawa J, Nishiyama M, Horinouchi S
TitleTyrosine 75 on the flap contributes to enhance catalytic efficiency of a fungal aspartic proteinase, Mucor pusillus pepsin.
[11]
PubMed ID9058201
JournalJ Biochem (Tokyo)
Year1997
Volume121
Pages118-21
AuthorsPark YN, Aikawa J, Nishiyama M, Horinouchi S, Beppu T
TitleSite-directed mutagenesis of conserved Trp39 in Rhizomucor pusillus pepsin: possible role of Trp39 in maintaining Tyr75 in the correct orientation for maximizing catalytic activity.
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
Medline ID97303051
PubMed ID9159482
JournalJ Mol Biol
Year1997
Volume268
Pages449-59
AuthorsYang J, Teplyakov A, Quail JW
TitleCrystal structure of the aspartic proteinase from Rhizomucor miehei at 2.15 A resolution.
Related PDB2asi
Related UniProtKBP00799
[13]
PubMed ID9561231
JournalAdv Exp Med Biol
Year1998
Volume436
Pages283-92
AuthorsQuail JW, Yang J, Schneider P, Jia Z
TitleCrystal structure of the Rhizomucor miehei aspartic proteinase.
[14]
CommentsX-ray crystallography
PubMed ID10089458
JournalActa Crystallogr D Biol Crystallogr
Year1999
Volume55
Pages625-30
AuthorsYang J, Quail JW
TitleStructure of the Rhizomucor miehei aspartic proteinase complexed with the inhibitor pepstatin A at 2.7 A resolution.
Related PDB2rmp
[15]
PubMed ID10744950
JournalBiotechnol Appl Biochem
Year2000
Volume31
Pages77-84
AuthorsBeldarrain A, Acosta N, Montesinos R, Mata M, Cremata J
TitleCharacterization of Mucor pusillus rennin expressed in Pichia pastoris: enzymic, spectroscopic and calorimetric studies.
[16]
PubMed ID11328603
JournalJ Biochem (Tokyo)
Year2001
Volume129
Pages791-4
AuthorsAikawa J, Park YN, Sugiyama M, Nishiyama M, Horinouchi S, Beppu T
TitleReplacements of amino acid residues at subsites and their effects on the catalytic properties of Rhizomucor pusillus pepsin, an aspartic proteinase from Rhizomucor pusillus.

comments
This enzyme belongs to the peptidae family-A1.
According to the literature [12], this enzyme has got a catalytic dyad composed of two aspartate residues, supporting the catalytic mechanism proposed by the paper [3].
Accoriding to the proposed mechanism (see [3]), the sidechains of both the aspartic acid residues are hydrogen-bonded to the catalytic water.
The sidechain of the ionized aspartate (possibly corresponding to Asp215 of 1mpp) might act as a general base, which can abstract a proton from the water, which in turn would make a nucleophilic attack on the carbonyl carbon of the peptide bond.
Meanwhile, the protonated sidechain of the other aspartate (corresponding to Asp32 of 1mpp) may stabilize the negative charge on the carbonyl oxygen of the scissile bond during the transition state.
At the next stage, the sidechain of the aspartate that had accepted a proton from water could protonate the leaving nitrogen atom, as a general acid, during the cleavage of the peptide bond.

createdupdated
2004-04-302012-06-28


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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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