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Crystallographic Studies of Native and Mutant Orotidine 5′phosphate Decarboxylases

  • Ning Wu
  • Emil F. Pai
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 238)

Abstract

This review aims to use the results of an approach combining crystallographic structure analysis with mutational studies as a framework for the various mechanistic proposals advanced in attempts to explain the astonishing acceleration rates displayed by orotidine 5′-monophosphate decarboxylase, the most proficient enzyme known. Special emphasis is placed on the contributions of active site amino acids to the selection and binding of substrate, product, and inhibitors as well as on the identification of alternative binding modes. Finally, a dynamic mechanism is proposed in which an increase in the strength of substrate binding and its catalytic conversion to product progress in parallel.

Keywords

X-ray crystallography Crystal structures Alternative binding modes Inhibitors Electrostatic strain Active site mutants Dynamic reaction mechanism Escherichia coli Bacillus subtilis Methanobacterium thermoautotrophicum Yeast 

Abbreviations

ODCase

Orotidine 5′-monophosphate decarboxylase

TIM

Triosephosphate isomerase

r.m.s.

Root-mean-square

BMP

6-hydroxyuridine 5′-mono-phosphate

CMP

Cytidine 5′-monophosphate

OMP

Orotidine 5′-monophosphate

UMP

Uridine 5′-monophosphate

XMP

Xanthine 5′-monophosphate

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Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of TorontoTorontoCanada
  2. 2.Division of Molecular & Structural BiologyOntario Cancer Institute/University Health NetworkTorontoCanada
  3. 3.Departments of Biochemistry, Medical Biophysics and Molecular & Medical GeneticsUniversity of TorontoTorontoCanada

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