Original Paper

Journal of Molecular Modeling

, Volume 14, Issue 8, pp 735-746

A dynamic view of enzyme catalysis

  • Aurora JiménezAffiliated withDepartament de Química de Pèptids i Proteïnes, Institut d´Investigacions Químiques i Ambientals de Barcelona (IIQAB–CSIC)
  • , Pere ClapésAffiliated withDepartament de Química de Pèptids i Proteïnes, Institut d´Investigacions Químiques i Ambientals de Barcelona (IIQAB–CSIC)
  • , Ramon CrehuetAffiliated withDepartament de Química de Pèptids i Proteïnes, Institut d´Investigacions Químiques i Ambientals de Barcelona (IIQAB–CSIC) Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Recent experimental advances have shown that enzymes are flexible molecules, and point to a direct link between dynamics and catalysis. Movements span a wide time range, from nano- to milli-seconds. In this paper we introduce two aspects of enzyme flexibility that are treated with two appropriate techniques. First, transition path sampling is used to obtain an unbiased picture of the transition state ensemble in chorismate mutase, as well as its local flexibility and the energy flow during the chemical step. Second, we consider the binding and release of substrates in L-rhamnulose-1-phosphate aldolase. We have calculated the normal modes of the enzyme with the elastic network model. The lowest frequency modes generate active site deformations that change the coordination number of the catalytic zinc ion. The coordination lability of zinc allows the binding and release of substrates. Substitution of zinc by magnesium blocks the exchange of ligands.

Keywords

Enzyme catalysis Enzyme dynamics Transition path sampling Energy relaxation QM/MM Chorismate mutase Aldolase