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Accession number;00A0163490
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| Title;Understanding the Reaction Mechanism of Class C .BETA.-Lactamase Using Model Compounds. |
| Author;
TOUMA YOKO
(Suntory Ltd.)
ISHIGURO MASAJI
(Suntory Ltd.)
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Journal Title;Abstracts. Symposium on Biofunctional Chemistry
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Journal Code:L0836A
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ISSN:
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VOL.14th;NO.;PAGE.62-63(1999)
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| Figure&Table&Reference; |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Many studies and a variety of approaches have been taken to gain a better understanding of the atomic-level mechanism of action of .BETA.-lactamases. With class C .BETA.-lactamase, X-ray crystallography has identified the active site structure and residues important for substrate recognition. Time-resolved IR difference spectroscopy has reassured the existence of the acylenzyme. Mutation studies as well as structural studies have suggested that either Tyr150 or Lys67 should function as a general base to the nucleophilic Ser64 in the formation of the acylenyzme. Since the identity of the general base in the acylation step still remains enigmatic, we have previously developed model compounds which mimic the key active site functionalities of class C .BETA.-lactamases, and have used them to measure the acidity of these functionalities. The results suggested a negatively charged Tyr150 residue, and positively charged Lys67 and Lys315 residues under physiological pH. In this context, we observed the reaction of the model compounds and their derivatives with two acylation agents in water (phosphate buffer, pH7.0). The results suggested that the phenolate is the general base in the amino acylation reaction. Extending this finding to the enzyme, it may be reasonable to think that Tyr150 is the general base in .BETA.-lactamase. (author abst.) |
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