Mechanisms and structures of crotonase superfamily enzymes – How nature controls enolate and oxyanion reactivity

Hamed, Refaat B.; Batchelar, Edward T.; Clifton, I.J.; Schofield, Christopher J.

doi:10.1007/s00018-008-8082-6

Cited by 111 publications

(152 citation statements)

References 132 publications

(189 reference statements)

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“…One such protein scaffold that correctly juxtaposes peptidic NH groups to form an oxyanion hole is referred to as a crotonase (or enoyl-CoA hydratase) fold after the enzyme for which it was first described. 65,66 Members of the crotonase superfamily contain a core domain of repeated bba motifs that form two parallel b-sheets situated at 90 with respect to each other. These b-sheets are surrounded by a-helices.…”

Section: Carboxyltransferase Domains With the Crotonase Foldmentioning

confidence: 99%

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

2012

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Biotin is the major cofactor involved in carbon dioxide metabolism. Indeed, biotindependent 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 CO 2 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 antiobesity 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 biotindependent enzymes. In addition, we provide a critical analysis of what these structures have and have not revealed about biotin-dependent catalysis.

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Section: Carboxyltransferase Domains With the Crotonase Foldmentioning

confidence: 99%

“…66 It is important to keep in mind that the mechanism presented in Figure 16 represents a starting point for subsequent investigations rather than the final word.…”

Section: Active Site Architecture and Substrate Bindingmentioning

confidence: 99%

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

2012

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“…5A). This bi-domain active site arrangement is common among members of the crotonase superfamily (47) and is characteristic for all structurally characterized biotin-dependent decarboxylases/carboxyltransferases (53).…”

Section: Resultsmentioning

confidence: 88%

An Asymmetric Model for Na+-translocating Glutaconyl-CoA Decarboxylases

Kress

Brügel

Schall

et al. 2009

Journal of Biological Chemistry

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Glutaconyl-CoA decarboxylase (Gcd) couples the biotin-dependent decarboxylation of glutaconyl-CoA with the generation of an electrochemical Na ؉ gradient. Sequencing of the genes encoding all subunits of the Clostridium symbiosum decarboxylase membrane complex revealed that it comprises two distinct biotin carrier subunits, GcdC 1 and GcdC 2 , which differ in the length of a central alanine-and proline-rich linker domain. Co-crystallization of the decarboxylase subunit GcdA with the substrate glutaconyl-CoA, the product crotonyl-CoA, and the substrate analogue glutaryl-CoA, respectively, resulted in a high resolution model for substrate binding and catalysis revealing remarkable structural changes upon substrate binding. Unlike the GcdA structure from Acidaminococcus fermentans, these data suggest that in intact Gcd complexes, GcdA is associated as a tetramer crisscrossed by a network of solventfilled tunnels.

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“…Group II C. botulinum has been shown to increase the unsaturated fatty acid content of its lipid membrane at low temperature (36), but the mechanisms for such adjustments are unclear. The cbo3202-encoded enzyme belongs to the crotonase superfamily, which harbors enzymes with diverse functions related to acyl-acyl carrier protein and acyl-CoA modifications-the central steps in lipid biosynthesis (37). Thus, a possible explanation for the markedly cold-sensitive phenotype exhibited by the cbo3202 mutant is that the putatively cbo3202-encoded 3-hydroxybutyryl-CoA dehydratase possesses an alternative function in fatty acid synthesis.…”

Section: Discussionmentioning

confidence: 99%

The Cold-Induced Two-Component System CBO0366/CBO0365 Regulates Metabolic Pathways with Novel Roles in Group I Clostridium botulinum ATCC 3502 Cold Tolerance

Dahlsten

Zhang

Somervuo

et al. 2014

Appl Environ Microbiol

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bThe two-component system CBO0366/CBO0365 was recently demonstrated to have a role in cold tolerance of group I Clostridium botulinum ATCC 3502. The mechanisms under its control, ultimately resulting in increased sensitivity to low temperature, are unknown. A transcriptomic analysis with DNA microarrays was performed to identify the differences in global gene expression patterns of the wild-type ATCC 3502 and a derivative mutant with insertionally inactivated cbo0365 at 37 and 15°C. Altogether, 150 or 141 chromosomal coding sequences (CDSs) were found to be differently expressed in the cbo0365 mutant at 37 or 15°C, respectively, and thus considered to be under the direct or indirect transcriptional control of the response regulator CBO0365. Of the differentially expressed CDSs, expression of 141 CDSs was similarly affected at both temperatures investigated, suggesting that the putative CBO0365 regulon was practically not affected by temperature. The regulon involved genes related to acetone-butanol-ethanol (ABE) fermentation, motility, arsenic resistance, and phosphate uptake and transport. Deteriorated growth at 17°C was observed for mutants with disrupted ABE fermentation pathway components (crt, bcd, bdh, and ctfA), arsenic detoxifying machinery components (arsC and arsR), or phosphate uptake mechanism components (phoT), suggesting roles for these mechanisms in cold tolerance of group I C. botulinum. Electrophoretic mobility shift assays showed recombinant CBO0365 to bind to the promoter regions of crt, arsR, and phoT, as well as to the promoter region of its own operon, suggesting direct DNA-binding transcriptional activation or repression as a means for CBO0365 in regulating these operons. The results provide insight to the mechanisms group I C. botulinum utilizes in coping with cold.

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Mechanisms and structures of crotonase superfamily enzymes – How nature controls enolate and oxyanion reactivity

Cited by 111 publications

References 132 publications

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

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

An Asymmetric Model for Na+-translocating Glutaconyl-CoA Decarboxylases

The Cold-Induced Two-Component System CBO0366/CBO0365 Regulates Metabolic Pathways with Novel Roles in Group I Clostridium botulinum ATCC 3502 Cold Tolerance

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Mechanisms and structures of crotonase superfamily enzymes – How nature controls enolate and oxyanion reactivity

Cited by 111 publications

References 132 publications

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

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

An Asymmetric Model for Na+-translocating Glutaconyl-CoA Decarboxylases

The Cold-Induced Two-Component System CBO0366/CBO0365 Regulates Metabolic Pathways with Novel Roles in Group I Clostridium botulinum ATCC 3502 Cold Tolerance

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

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