Ribonucleotide activation by enzyme ribonucleotide reductase: Understanding the role of the enzyme

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Cerqueira, NMFSA (Author) Other; Fernandes, PA (Author) FCUP; Eriksson, LA (Author) Other; Ramos, MJ (Author) FCUP

Journal

Title: Journal of Computational Chemistry

Vol. 25

Pages: 2031-2037

ISSN: 0192-8651

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 31 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-7HN

DOI: 10.1002/jcc.20127

Abstract (EN): This article focuses on the first step of the catalytic mechanism for the reduction of ribonucleotides catalyzed by the enzyme Ribonucleoticle Reductase (RNR). This corresponds to the activation of the substrate. In this work a large model of the active site region involving 130 atoms was used instead of the minimal gas phase models used in previous works. The ONIOM method was employed to deal with such a large system. The results gave additional information, which previous small models could not provide, allowing a much clearer evaluation of the role of the enzyme in this step. Enzyme-substrate interaction energies, specific transition state stabilization, and substrate steric strain energies were obtained. It was concluded that the transition state is stabilized in 4.0 kcal/mol by specific enzyme-substrate interactions. However, this stabilization is cancelled by the cost in conformational energy for the enzyme to adopt the transition state geometry; the overall result is that the enzyme machinery does not lead to a rate enhancement in this step. It was also found that the substrate binds to the active site with almost no steric strain, emphasizing the complementarity and specificity of the RNR active site for nucleotide binding. The main role of the enzyme at the very beginning of the catalytic cycle was concluded to be to impose stereospecifity upon substrate activation and to protect the enzyme radical from the solvent, rather than to be an reaction rate enhancement. (C) 2004 Wiley Periodicals, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7