PMID:16104732
| Citation |
Iwig, DF, Uchida, A, Stromberg, JA and Booker, SJ (2005) The activity of Escherichia coli cyclopropane fatty acid synthase depends on the presence of bicarbonate. J. Am. Chem. Soc. 127:11612-3 |
|---|---|
| Abstract |
Cyclopropane fatty acid (CFA) synthases catalyze the formation of cyclopropane rings on isolated and unactivated olefinic bonds within various fatty acids; the methylene carbon is derived from the activated methyl group of (S)-adenosylmethionine. The E. coli enzyme is the prototype for this class of enzymes, which include the cyclopropane mycolic acid (CMA) synthases, which are potential targets for the design of antituberculosis agents. Crystal structures of several CMA synthases have recently been solved, and electron density attributed to a bicarbonate ion was found in or near the active site. Because a functional assay for CMA synthases has not been developed, the relevance of the bicarbonate ion has not been established. CFA synthase is 30-35% identical to the CMA synthases that have been analyzed structurally, suggesting that the mechanisms of these enzymes are conserved. In this work, we show that indeed the activity of CFA synthase requires bicarbonate, and that it is inhibited by borate, a planar trigonal molecule that mimics the structure of bicarbonate. We also show that substitutions of the conserved amino acids that act as ligands to the bicarbonate ion based on the structure of CMA synthases result in drastic losses in the activity of the protein. |
| Links |
PubMed Online version:10.1021/ja053899z |
| Keywords |
Bicarbonates/chemistry; Bicarbonates/pharmacology; Escherichia coli/enzymology; Methyltransferases/chemistry; Methyltransferases/drug effects; Methyltransferases/metabolism; Molecular Structure |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.