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Orotidine Monophosphate Decarboxylase pp 63–78Cite as

Survey of Enzymological Data on ODCase

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Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 238))

Abstract

OMP decarboxylase (ODCase) has been the subject of enzymological, structural, and theoretical studies for several decades, yet its highly proficient rate of decarboxylation remains mechanistically unclear. This review summarizes the enzymological and model studies carried out with ODCase and its substrate analogs. The original mechanism involving protonation of O2 of the substrate OMP by an enzyme functional group has gained some experimental support, including the measurement of isotope effects, affinities of various inhibitors, and catalytic activity or inactivity toward alternate substrates. A lysine residue of the yeast enzyme, Lys93, invariant in all known sequences and situated within a region of the sequence that is highly similar throughout all sequences, has been proposed to be the active site proton donor. However, the crystal structures of ODCase in complex with various inhibitors show the 5,6 side of the pyrimidine of the inhibitors in proximity with the active site lysine side chain, with O2 turned away from the lysine. The enzymological data is reconciled with the structural data in this review with the proposal that the nearly symmetrical inhibitors bind in an orientation that is reversed from that of the substrate, with the glycosidic bond rotated roughly 180° from that projected for the substrate.

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Abbreviations

6-azaUMP :

6-Azauridine-5′-monophosphate

BMP :

1-(5′-Phospho-β-d-ribofuranosyl)barbituric acid

OMP :

Orotidine-5′-monophosphate

2-thioOMP :

2-Thioorotidine-5′-monophosphate

UMP :

Uridine-5′-monophosphate

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Acknowledgements

Research in the author’s laboratory is funded by NIH Grant R15 GM63504-01, the Youngstown State University Presidential Academic Center for Excellence in Research, and the Ohio Board of Regents Hayes Investment Fund. The ongoing collaboration with Raelene Lawrence, Chemical Computing Group , Montreal, is gratefully acknowledged, as are collaborations with other ODCase investigators.

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  1. Department of Chemistry, Youngstown State University, Youngstown, OH , 44555 , USA

    Jeffrey A. Smiley

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  1. Jeffrey A. Smiley
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Correspondence to Jeffrey A. Smiley .

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J.K. Lee

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Smiley, J.A. Survey of Enzymological Data on ODCase. In: Lee, J. (eds) Orotidine Monophosphate Decarboxylase. Topics in Current Chemistry, vol 238. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b94539

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  • DOI: https://doi.org/10.1007/b94539

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-20566-1

  • Online ISBN: 978-3-540-40039-4

  • eBook Packages: Springer Book Archive

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