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http://purl.uniprot.org/citations/11080627http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11080627http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11080627http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Citation
http://purl.uniprot.org/citations/11080627http://www.w3.org/2000/01/rdf-schema#comment"

Background

Semisynthetic cephalosporins are primarily synthesized from 7-aminocephalosporanic acid (7-ACA), which is usually obtained by chemical deacylation of cephalosporin C (CPC). The chemical production of 7-ACA includes, however, several expensive steps and requires thorough treatment of chemical wastes. Therefore, an enzymatic conversion of CPC to 7-ACA by cephalosporin acylase is of great interest. The biggest obstacle preventing this in industrial production is that cephalosporin acylase uses glutaryl-7ACA as a primary substrate and has low substrate specificity for CPC.

Results

We have solved the first crystal structure of a cephalosporin acylase from Pseudomonas diminuta at 2.0 A resolution. The overall structure looks like a bowl with two "knobs" consisting of helix- and strand-rich regions, respectively. The active site is mostly formed by the distinctive structural motif of the N-terminal (Ntn) hydrolase superfamily. Superposition of the 61 residue active-site pocket onto that of penicillin G acylase shows an rmsd in Calpha positions of 1.38 A. This indicates structural similarity in the active site between these two enzymes, but their overall structures are elsewhere quite different.

Conclusion

The substrate binding pocket of the P. diminuta cephalosporin acylase provides detailed insight into the ten key residues responsible for the specificity of the cephalosporin C side chain in four classes of cephalosporin acylases, and it thereby forms a basis for the design of an enzyme with an improved conversion rate of CPC to 7-ACA. The structure also provides structural evidence that four of the five different classes of cephalosporin acylases can be grouped into one family of the Ntn hydrolase superfamily."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)00505-0"xsd:string
http://purl.uniprot.org/citations/11080627http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(00)00505-0"xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Kim Y."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Kim Y."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Hol W.G.J."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Hol W.G.J."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Turley S."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Turley S."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Yoon K.-H."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Yoon K.-H."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Khang Y."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/author"Khang Y."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/pages"1059-1068"xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/pages"1059-1068"xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/title"The 2.0 A crystal structure of cephalosporin acylase."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/title"The 2.0 A crystal structure of cephalosporin acylase."xsd:string
http://purl.uniprot.org/citations/11080627http://purl.uniprot.org/core/volume"8"xsd:string
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