The contribution of key hydrophobic residues in ecotin to enzyme-inhibitor complex stability

Maelíosa T C McCrudden, Louise A. Ryan, Philip Turkington, David J. Timson

Research output: Contribution to journalArticlepeer-review

Abstract

The Escherichia coli protease inhibitor ecotin is believed to be implicated in the evasion of host defenses during infection. The protein has also attracted attention as a scaffold for the design of novel, specific protease inhibitors. Ecotin interacts with its targets through two sites. Key hydrophobic residues in both sites (Leu-64, Trp-67, Tyr-69, Met-84, and Met-85) were mutated to alanine and the effects on the inhibition of trypsin, chymotrypsin, and elastase were assessed. Each of these mutant ecotin proteins tested in kinetic assays with these enzymes exerted less inhibitory potency compared to wild-type ecotin. However, these effects were relatively small and not additive.

Original languageEnglish
Pages (from-to)1207-1210
Number of pages4
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume24
Issue number6
DOIs
Publication statusPublished - 1 Dec 2009

Keywords

  • Alanine substitution
  • Chymotrypsin
  • Elastase
  • Free energy of interaction
  • Protease inhibitor
  • Trypsin

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