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

Evette S Radisky, Justin M. Lee, C. J K Lu, Daniel E. Koshland

Research output: Contribution to journalArticle

85 Citations (Scopus)

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

Fingerprint

Acylation
Serine Proteases
Catalysis
Histidine
Trypsin
Serine
Catalytic Domain
Water
Enzymes

Keywords

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

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates. / Radisky, Evette S; Lee, Justin M.; Lu, C. J K; Koshland, Daniel E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 18, 02.05.2006, p. 6835-6840.

Research output: Contribution to journalArticle

@article{4506e085071b4b92a6440399990ef90d,
title = "Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates",
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.",
keywords = "Acyl-enzyme, Enzyme mechanism, Reaction trajectory, Steady state",
author = "Radisky, {Evette S} and Lee, {Justin M.} and Lu, {C. J K} and Koshland, {Daniel E.}",
year = "2006",
month = "5",
day = "2",
doi = "10.1073/pnas.0601910103",
language = "English (US)",
volume = "103",
pages = "6835--6840",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

TY - JOUR

T1 - Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates

AU - Radisky, Evette S

AU - Lee, Justin M.

AU - Lu, C. J K

AU - Koshland, Daniel E.

PY - 2006/5/2

Y1 - 2006/5/2

N2 - 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.

AB - 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.

KW - Acyl-enzyme

KW - Enzyme mechanism

KW - Reaction trajectory

KW - Steady state

UR - http://www.scopus.com/inward/record.url?scp=33646489776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646489776&partnerID=8YFLogxK

U2 - 10.1073/pnas.0601910103

DO - 10.1073/pnas.0601910103

M3 - Article

C2 - 16636277

AN - SCOPUS:33646489776

VL - 103

SP - 6835

EP - 6840

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -