| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Citation |
| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/2000/01/rdf-schema#comment | "Carbapenam synthetase (hereafter named CPS) catalyzes the formation of the beta-lactam ring in the biosynthetic pathway to (5R)-carbapen-2-em-3-carboxylate, the simplest of the carbapenem antibiotics. Kinetic studies showed remarkable tolerance to substrate stereochemistry in the turnover rate but did not distinguish between chemistry and a nonchemical step such as product release or conformational change as being rate-determining. Also, X-ray structural studies and modest sequence homology to beta-lactam synthetase, an enzyme that catalyzes the formation of a monocyclic beta-lactam ring in a similar ATP/Mg2+-dependent reaction, implicate K443 as an essential residue for substrate binding and intermediate stabilization. In these experiments, we use pH-rate profiles, deuterium solvent isotope effects, and solvent viscosity measurements to examine the rate-limiting step in this complex overall process of substrate adenylation and intramolecular ring formation. Mutagenesis and chemical rescue demonstrate that K443 is the general acid visible in the pH-rate profile of the wild-type CPS-catalyzed reaction. On the basis of these results, we propose a mechanism in which the rate-limiting step is beta-lactam ring formation coupled to a protein conformational change and underscore the role of K443 throughout the reaction."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi0618464"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi0618464"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/author | "Townsend C.A."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/author | "Townsend C.A."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/author | "Arnett S.O."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/author | "Arnett S.O."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/author | "Gerratana B."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/author | "Gerratana B."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/pages | "9337-9345"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/pages | "9337-9345"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/title | "Rate-limiting steps and role of active site Lys443 in the mechanism of carbapenam synthetase."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/title | "Rate-limiting steps and role of active site Lys443 in the mechanism of carbapenam synthetase."xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/volume | "46"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://purl.uniprot.org/core/volume | "46"xsd:string |
| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17658887 |
| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17658887 |
| http://purl.uniprot.org/citations/17658887 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17658887 |