The three-dimensional structure of Asn102 mutant of trypsin: role of Asp102 in serine protease catalysis

Science. 1987 Aug 21;237(4817):905-9. doi: 10.1126/science.3112942.


The structure of the Asn102 mutant of trypsin was determined in order to distinguish whether the reduced activity of the mutant at neutral pH results from an altered active site conformation or from an inability to stabilize a positive charge on the active site histidine. The active site structure of the Asn102 mutant of trypsin is identical to the native enzyme with respect to the specificity pocket, the oxyanion hole, and the orientation of the nucleophilic serine. The observed decrease in rate results from the loss of nucleophilicity of the active site serine. This decreased nucleophilicity may result from stabilization of a His57 tautomer that is unable to accept the serine hydroxyl proton.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asparagine
  • Aspartic Acid
  • Binding Sites
  • Cattle
  • Computer Simulation
  • Crystallography
  • Histidine
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Protein Conformation
  • Rats
  • Serine
  • Structure-Activity Relationship
  • Trypsin*


  • Aspartic Acid
  • Serine
  • Histidine
  • Asparagine
  • Trypsin