Research Article

Systematic comparison of catalytic mechanisms of hydrolysis and transfer reactions classified in the EzCatDB database

  1. Nozomi Nagano1,2,*,
  2. Tamotsu Noguchi1,
  3. Yutaka Akiyama1

Article first published online: 12 OCT 2006

DOI: 10.1002/prot.21193

Issue

Proteins: Structure, Function, and Bioinformatics

Proteins: Structure, Function, and Bioinformatics

Volume 66, Issue 1, pages 147–159, January 2007

Additional Information

How to Cite

Nagano, N., Noguchi, T. and Akiyama, Y. (2007), Systematic comparison of catalytic mechanisms of hydrolysis and transfer reactions classified in the EzCatDB database. Proteins: Structure, Function, and Bioinformatics, 66: 147–159. doi: 10.1002/prot.21193

Author Information

  1. 1

    Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan

  2. 2

    PRESTO, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 332-0012, Japan

*Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan

Publication History

  1. Issue published online: 6 DEC 2006
  2. Article first published online: 12 OCT 2006
  3. Manuscript Accepted: 2 AUG 2006
  4. Manuscript Revised: 27 JUL 2006
  5. Manuscript Received: 2 DEC 2005

Funded by

  • PRESTO (organized by the Japan Science and Technology Corporation (JST))
  • Scientific Research (B) (organized by the Japan Society for the Promotion of Science (JSPS))

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (624K)

Keywords:

  • enzyme catalytic functions;
  • enzyme structures;
  • hydrolases;
  • Transferases

Abstract

Catalytic mechanisms of 270 enzymes from 131 superfamilies, mainly hydrolases and transferases, were analyzed based on their enzyme structures. A method of systematic comparison and classification of the catalytic reactions was developed. Hydrolysis and transfer reactions closely resemble one another, displaying common mechanisms, single displacement, and double displacement. These displacement mechanisms might be further subclassified according to the type of catalytic factors and nucleophilic substitution involved. Several types of catalytic factors exist: nucleophile, acid, base, stabilizer, modulator, cofactors. Nucleophilic substitution might be categorized as SN1/SN2 (or dissociative/associative) reactions. The classification indicates that some mechanisms favor particular types of catalytic factors. In hydrolyses of amide bonds and phosphoric ester bonds, mechanisms with single displacement tend to use inorganic cofactors such as zinc and magnesium ions as important catalysts, whereas those with double displacement frequently do not use such cofactors. In contrast, hydrolyses of O-glycoside bond rarely use such cofactors, with one exception. The trypsin-like hydrolytic reaction, which is catalyzed by the classic catalytic triad comprising serine/histidine/aspartate, can be considered as a “super-reaction” because it is observed in at least three nonhomologous enzymes, whereas most reactions are singlets without any nonhomologous enzymes. By dividing complex reactions into several reactions, correlations between active site structures and catalytic functions can be suggested. This classification method is applicable to other reactions such as elimination and isomerization. Furthermore, it will facilitate annotation of enzyme functions from 3D patterns of enzyme active sites. The classification is available at http://mbs.cbrc.jp/EzCatDB/RLCP/index.html. Proteins 2007. ©2006 Wiley-Liss, Inc.

View Full Article with Supporting Information (HTML) Get PDF (624K)