biostudies-literatureRodkey EANIAID NIH HHSNIGMS NIH HHS18358-69https://www.ebi.ac.uk/biostudies/studies/S-EPMC4042847biostudies-literatureUnknown135(49)The inhibition of the class A SHV-1 β-lactamase by 7-(tert-butoxycarbonyl)methylidenecephalosporin sulfone was examined kinetically, spectroscopically, and crystallographically. An 1.14 Å X-ray crystal structure shows that the stable acyl-enzyme, which incorporates an eight-membered ring, is a covalent derivative of Ser70 linked to the 7-carboxy group of 2-H-5,8-dihydro-1,1-dioxo-1,5-thiazocine-4,7-dicarboxylic acid. A cephalosporin-derived enzyme complex of this type is unprecedented, and the rearrangement leading to its formation may offer new possibilities for inhibitor design. The observed acyl-enzyme derives its stability from the resonance stabilization conveyed by the β-aminoacrylate (i.e., vinylogous urethane) functionality as there is relatively little interaction of the eight-memJournal of the American Chemical Societyβ-Lactamase inhibition by 7-alkylidenecephalosporin sulfones: allylic transposition and formation of an unprecedented stabilized acyl-enzyme.PMC4042847R01AI072219R01AI100560R01 AI063517R01 AI100560GM54072R01AI063517R01 AI062968R56 GM054072AI062968R01 GM054072R01 AI072219R56 AI062968Carey PRChe TBuynak JDBethel CRSmith KMMcLeod DCvan den Akker FRodkey EABonomo RAXu YChai Wfalseβ-Lactamase inhibition by 7-alkylidenecephalosporin sulfones: allylic transposition and formation of an unprecedented stabilized acyl-enzyme.The inhibition of the class A SHV-1 β-lactamase by 7-(tert-butoxycarbonyl)methylidenecephalosporin sulfone was examined kinetically, spectroscopically, and crystallographically. An 1.14 Å X-ray crystal structure shows that the stable acyl-enzyme, which incorporates an eight-membered ring, is a covalent derivative of Ser70 linked to the 7-carboxy group of 2-H-5,8-dihydro-1,1-dioxo-1,5-thiazocine-4,7-dicarboxylic acid. A cephalosporin-derived enzyme complex of this type is unprecedented, and the rearrangement leading to its formation may offer new possibilities for inhibitor design. The observed acyl-enzyme derives its stability from the resonance stabilization conveyed by the β-aminoacrylate (i.e., vinylogous urethane) functionality as there is relatively little interaction of the eight-mem2013-01-01T00:00:00Z2013 Dec2026-04-29T11:45:12.702Z2026-04-14T03:07:01.589ZS-EPMC40428472421931310.1021/ja403598g