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

Evette S. Radisky, Justin M. Lee, Chia Jung Karen Lu, Daniel E. Koshland

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6835-6840
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number18
DOIs
StatePublished - May 2 2006

Keywords

  • Acyl-enzyme
  • Enzyme mechanism
  • Reaction trajectory
  • Steady state

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates'. Together they form a unique fingerprint.

  • Cite this