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PMID: 3456162 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The nature of enzyme catalysis in trypsin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 3 ·1986-02-00 ·Pages 649-53

Weiner SJ, Seibel GL, Kollman PA

Abstract

We present a combined quantum/molecular mechanical study of the trypsin-catalyzed hydrolysis of a specific tripeptide substrate, including the entire enzyme in the calculation, as well as 200 H2O molecules. The results illustrate how the enzyme and nearby H2O molecules stabilize the ionic intermediates in peptide hydrolysis, such that the reaction is calculated to have a barrier that is significantly smaller than the calculated and experimental base-catalyzed barrier of formamide hydrolysis in aqueous solution. This enables us to understand how serine proteases increase the rates for reactions that take place in their active sites, compared to the corresponding rates for analogous solution reactions.

MeSH Terms

Binding Sites Catalysis Histidine Hydrolysis Models, Chemical Quantum Theory Trypsin/metabolism

Chemicals

Histidine Trypsin

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Weiner S J

Seibel G L

Kollman P A

References (13)

13 references, click to expand

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Article Info

Journal

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

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.83.3.649

Published

1986-02-00

Pages

649-53

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC322921

Subset

Grants

NIGMS NIH HHS · GM-29072 · United States

NCRR NIH HHS · RR-1081 · United States

External Links

PubMed source DOI: 10.1073/pnas.83.3.649 PMC Full Text View journal details

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The nature of enzyme catalysis in trypsin.

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