EzCatDB: S00513
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DB codeS00513
RLCP classification1.13.29990.17 : Hydrolysis
CATH domainDomain 13.40.710.10 : Beta-lactamaseCatalytic domain
E.C.3.5.2.6

CATH domainRelated DB codes (homologues)
3.40.710.10 : Beta-lactamaseS00512,S00529,S00414,T00222

Enzyme Name
UniProtKBKEGG

P14489
Protein nameBeta-lactamase OXA-10beta-lactamase
penicillinase
cephalosporinase
neutrapen
penicillin beta-lactamase
exopenicillinase
ampicillinase
penicillin amido-beta-lactamhydrolase
penicillinase I, II
beta-lactamase I-III
beta-lactamase A, B, C
beta-lactamase AME I
cephalosporin-beta-lactamase
SynonymsEC 3.5.2.6
Beta-lactamase PSE-2
PfamPF00905 (Transpeptidase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00311Penicillin and cephalosporin biosynthesis
MAP00312beta-Lactam resistance

UniProtKB:Accession NumberP14489
Entry nameBLO10_PSEAE
ActivityA beta-lactam + H(2)O = a substituted beta- amino acid.
Subunit
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC01866C00395C00875C00001C03806
Compoundbeta-LactamPenicillinCephalosporinH2OSubstituted beta-amino acid
Typeamide groupamide group,carboxyl group,sulfide groupamide group,amine group,carboxyl group,sulfide groupH2Oamino acids
ChEBI


15377

PubChem


962
22247451

             
1e3uAUnboundUnboundUnbound Unbound
1e3uBUnboundUnboundUnbound Unbound
1e3uCUnboundUnboundUnbound Unbound
1e3uDUnboundUnboundUnbound Unbound
1e4dAUnboundUnboundUnbound Unbound
1e4dBUnboundUnboundUnbound Unbound
1e4dCUnboundUnboundUnbound Unbound
1e4dDUnboundUnboundUnbound Unbound
1ewzAUnboundUnboundUnbound Unbound
1ewzBUnboundUnboundUnbound Unbound
1ewzCUnboundUnboundUnbound Unbound
1ewzDUnboundUnboundUnbound Unbound
1fofAUnboundUnboundUnbound Unbound
1fofBUnboundUnboundUnbound Unbound

Active-site residues
resource
literature [3]
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
            
1e3uASER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1e3uBSER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1e3uCSER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1e3uDSER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1e4dASER 67;TRP 154
KCX 70(Carbamylation)
SER 67;PHE 208
carbamated Lys70
1e4dBSER 67;TRP 154
KCX 70(Carbamylation)
SER 67;PHE 208
carbamated Lys70
1e4dCSER 67;TRP 154
KCX 70(Carbamylation)
SER 67;PHE 208
carbamated Lys70
1e4dDSER 67;TRP 154
KCX 70(Carbamylation)
SER 67;PHE 208
carbamated Lys70
1ewzASER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1ewzBSER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1ewzCSER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1ewzDSER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1fofASER 67;TRP 154
LYS 70
SER 67;PHE 208
 
1fofBSER 67;TRP 154
LYS 70
SER 67;PHE 208
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.6133
[2]p.922-924
[3]p.1292-1296
[4]p.2463, Scheme 12

references
[1]
JournalJ Am Chem Soc
Year2000
Volume122
Pages6132-3
AuthorsGolemi D, Maveyraud L, Vakulenko S, Tranier S, Ishiwata A, Kotra LP, Samama JP, Mobashery S
TitleThe first structural and mechanistic insights for class d beta-lactamases: evidence for a novel catalytic process for turnover of beta-lactam antibiotics.
Related PDB1ewz
[2]
CommentsX-ray crystallography (2.0 Angstroms)
PubMed ID11017203
JournalNat Struct Biol
Year2000
Volume7
Pages918-25
AuthorsPaetzel M, Danel F, de Castro L, Mosimann SC, Page MG, Strynadka NC
TitleCrystal structure of the class D beta-lactamase OXA-10.
Related PDB1fof
[3]
CommentsX-ray crystallography (1.66 Angstroms)
Medline ID21029090
PubMed ID11188693
JournalStructure Fold Des
Year2000
Volume8
Pages1289-98
AuthorsMaveyraud L, Golemi D, Kotra LP, Tranier S, Vakulenko S, Mobashery S, Samama JP
TitleInsights into class D beta-lactamases are revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa.
Related PDB1e3u,1e4d
Related UniProtKBP14489
[4]
PubMed ID11890794
JournalJ Am Chem Soc
Year2002
Volume124
Pages2461-5
AuthorsMaveyraud L, Golemi-Kotra D, Ishiwata A, Meroueh O, Mobashery S, Samama JP
TitleHigh-resolution X-ray structure of an acyl-enzyme species for the class D OXA-10 beta-lactamase.

comments
This enzyme belongs to the class-D beta-lactamase family.
This enzyme is also a serine hydrolase, in which Ser67 acts as a nucleophile to form acyl-enzyme intermediate ([1], [2], [3] & [4]).
In the early studies ([1] & [2]), although Lys70 was a possible candidate for the general base to activate a hydrolytic water in deacylation, the catalytic mechanism has remained to be elucidated. In more recent papers ([3] & [4]), it was reported that the lysine residue is carbamated, and that this carbamate acts as a general base, which can activate the nucleophilic Ser67 in the acylation step, and then, a water molecule in the deacylation step. According to the literature [4], the carbamate of Lys is modulated by Trp154, whereas mainchain amide groups of Ser67 and Phe208 (along with sidechain of Ser115) form an oxyanion hole as stabilizers.
Thus, the reaction proceeds as follows:
(1) Trp154 modulates the activity of carbamated Lys70.
(2) The carbamated Lys70 acts as a general base to deprotonate Ser67.
(3) Ser67 makes a nucleophilic attack on amide bond, forming acyl intermediate. (Here, the carbamated Lys70 must act as a general acid to protonate the leaving amine group. Otherwise, it can act as a general base in deacylation step.)
(4) The intermediate is stablized by an oxyanion hole, composed of mainchain amide of Ser67 and Phe208.
(5) The carbamated Lys70 acts as a general base again, to activate a water.
(6) The activated water makes a nucleophilic attack on the acyl intermediate.
(7) The carbamated Lys70 may act as a general acid again, to protonate Ser67.

createdupdated
2002-09-272009-02-26


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