Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9

Lillian T. Chong, Pradipta Bandyopadhyay, Thomas S. Scanlan, Irwin D. Kuntz, Peter A. Kollman

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Direct hydroxide attack on the scissile carbonyl of the substrate has been suggested as a likely mechanism for esterase antibodies elicited by phosphonate haptens, which mimic the transition states for the alkaline hydrolysis of esters. The unique amidase activity of esterase antibody 43C9 has been attributed to nucleophilic attack by an active-site histidine residue. Yet, the active site of 43C9 is strikingly similar to those of other esterase antibodies, particularly 17E8. We have carried out quantum mechanical calculations, molecular dynamics simulations, and free energy calculations to assess the mechanism involving direct hydroxide attack for 43C9. Results support this mechanism and suggest that the mechanism is plausible for other antiphosphonate antibodies that catalyze the hydrolysis of (p-nitro)phenyl esters.

Original languageEnglish (US)
Pages (from-to)1371-1377
Number of pages7
JournalJournal of Computational Chemistry
Volume24
Issue number12
DOIs
StatePublished - Sep 1 2003

Keywords

  • Amide/ester hydrolysis
  • Catalytic antibodies
  • Free energy calculations
  • Molecular dynamics simulations
  • Quantum mechanical calculations

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

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