Serine peptidase catalytic machinery: Cooperative one-step mechanism

✍ Scribed by G. Dive; D. Dehareng

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 268 KB
• Volume: 73
• Category: Article
• ISSN: 0020-7608
• DOI: 10.1002/(sici)1097-461x(1999)73:2<161::aid-qua10>3.0.co;2-e

✦ Synopsis

The acylation reaction of ␤-lactamases by ␤-lactam compounds is modeled as a one-step process. Twenty seven transition-state models are investigated at Ž . the restricted Hartree᎐Fock RHF level within the minimal MINI-1Ј basis set. These transition states differ by the nature of both the substrate and the amino acids constituting the reactive nucleophile. The intrinsic reactivity of the class-A and class-C ␤-lactamases are under concern. Eight transition-state models were docked in a class-A ␤-lactamase, TEM1, as optimized with the benzylpenicillin at the molecular mechanics level. In the proposed one-step acylation process, only two amino acids are directly involved, the usual nucleophilic serine, S70 in TEM1, and a close serine or tyrosine, S130 in TEM1, Y150 in P99. The lysine close to these two residues, K73 in TEM1, plays only an indirect role in the process.