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Keywords:

  • serine protease;
  • bovine pancreatic β-trypsin;
  • anti-pancreatitis drug;
  • gabexate mesilate;
  • 6-guanidinohexanoyl trypsin;
  • optimum pH for catalysis;
  • catalytic water;
  • Bürgi-Dunitz angle;
  • Ethyl-4-hydroxybenzoate;
  • X-ray crystal structure

Abstract

The force driving the conversion from the acyl intermediate to the tetrahedral intermediate in the deacylation reaction of serine proteases remains unclear. The crystal structure of 6-guanidinohexanoyl trypsin was determined at pH 7.0, near the optimum reaction pH, at 1.94 Å resolution. In this structure, three water molecules are observed around the catalytic site. One acts as a nucleophile to attack the acyl carbonyl carbon while the other two waters fix the position of the catalytic water through a hydrogen bond. When the acyl carbonyl oxygen oscillates thermally, the water assumes an appropriate angle to catalyze the deacylation. Proteins 2013. © 2012 Wiley Periodicals, Inc.