1. Academic Validation
  2. Malate dehydrogenase: a model for structure, evolution, and catalysis

Malate dehydrogenase: a model for structure, evolution, and catalysis

  • Protein Sci. 1994 Oct;3(10):1883-8. doi: 10.1002/pro.5560031027.
C R Goward 1 D J Nicholls
Affiliations

Affiliation

  • 1 Centre for Applied Microbiology and Research, Salisbury, United Kingdom.
Abstract

Malate dehydrogenases are widely distributed and alignment of the amino acid sequences show that the Enzyme has diverged into 2 main phylogenetic groups. Multiple amino acid sequence alignments of malate dehydrogenases also show that there is a low degree of primary structural similarity, apart from in several positions crucial for nucleotide binding, catalysis, and the subunit interface. The 3-dimensional structures of several malate dehydrogenases are similar, despite their low amino acid sequence identity. The coenzyme specificity of malate dehydrogenase may be modulated by substitution of a single residue, as can the substrate specificity. The mechanism of catalysis of malate dehydrogenase is similar to that of Lactate Dehydrogenase, an Enzyme with which it shares a similar 3-dimensional structure. Substitution of a single amino acid residue of a Lactate Dehydrogenase changes the Enzyme specificity to that of a malate dehydrogenase, but a similar substitution in a malate dehydrogenase resulted in relaxation of the high degree of specificity for oxaloacetate. Knowledge of the 3-dimensional structures of malate and lactate dehydrogenases allows the redesign of Enzymes by rational rather than random mutation and may have important commercial implications.

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