1. Academic Validation
  2. Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates

Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates

  • Proc Natl Acad Sci U S A. 2006 May 2;103(18):6835-40. doi: 10.1073/pnas.0601910103.
Evette S Radisky 1 Justin M Lee Chia-Jung Karen Lu Daniel E Koshland Jr
Affiliations

Affiliation

  • 1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Abstract

Atomic resolution structures of trypsin acyl-enzymes and a tetrahedral intermediate analog, along with previously solved structures representing the Michaelis complex, are used to reconstruct events in the catalytic cycle of this classic serine protease. Structural comparisons provide insight into active site adjustments involved in catalysis. Subtle motions of the catalytic serine and histidine residues coordinated with translation of the substrate reaction center are seen to favor the forward progress of the acylation reaction. The structures also clarify the attack trajectory of the hydrolytic water in the deacylation reaction.

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