The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

Biotin is the major cofactor involved in carbon dioxide metabolism. Indeed, biotin‐dependent enzymes are ubiquitous in nature and are involved in a myriad of metabolic processes including fatty acid synthesis and gluconeogenesis. The cofactor, itself, is composed of a ureido ring, a tetrahydrothioph...

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Bibliographic Details
Published in:Protein science 2012-11, Vol.21 (11), p.1597-1619
Main Authors: Waldrop, Grover L., Holden, Hazel M., Maurice, Martin St
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - chemistry
Adenosine Triphosphate - metabolism
Animals
ATP‐grasp superfamily of enzymes
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Binding Sites
biotin
Biotin - chemistry
Biotin - metabolism
biotin‐dependent enzymes
Carbon dioxide
Carbon Dioxide - chemistry
Carbon Dioxide - metabolism
Carboxy-Lyases - chemistry
Carboxy-Lyases - metabolism
Carboxyl and Carbamoyl Transferases - chemistry
Carboxyl and Carbamoyl Transferases - metabolism
carboxylases
Catalysis
CO2 metabolism
crotonase superfamily of enzymes
decarboxylases
Enzymes
Humans
Metabolism
Models, Molecular
Protein Conformation
Reviews
transcarboxylases
vitamin B7
vitamin H
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Summary:Biotin is the major cofactor involved in carbon dioxide metabolism. Indeed, biotin‐dependent enzymes are ubiquitous in nature and are involved in a myriad of metabolic processes including fatty acid synthesis and gluconeogenesis. The cofactor, itself, is composed of a ureido ring, a tetrahydrothiophene ring, and a valeric acid side chain. It is the ureido ring that functions as the CO2 carrier. A complete understanding of biotin‐dependent enzymes is critically important for translational research in light of the fact that some of these enzymes serve as targets for anti‐obesity agents, antibiotics, and herbicides. Prior to 1990, however, there was a dearth of information regarding the molecular architectures of biotin‐dependent enzymes. In recent years there has been an explosion in the number of three‐dimensional structures reported for these proteins. Here we review our current understanding of the structures and functions of biotin‐dependent enzymes. In addition, we provide a critical analysis of what these structures have and have not revealed about biotin‐dependent catalysis.
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.2156