Abstract
Malonyl-CoA-acyl carrier protein transacylase (MCAT) transfers the malonyl group from malonyl-CoA to holo-acyl carrier protein (ACP), and since malonyl-ACP is a key building block for fatty-acid biosynthesis it is considered as a promising antibacterial target. The crystal structures of MCAT from Staphylococcus aureus and Streptococcus pneumoniae have been determined at 1.46 and 2.1A resolution, respectively. In the SaMCAT structure, the N-terminal expression peptide of a neighboring molecule running in the opposite direction of malonyl-CoA makes extensive interactions with the highly conserved "Gly-Gln-Gly-Ser-Gln" stretch, suggesting a new design platform. Mutagenesis results suggest that Ser91 and His199 are the catalytic dyad.
Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyl-Carrier Protein S-Malonyltransferase / antagonists & inhibitors*
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Acyl-Carrier Protein S-Malonyltransferase / chemistry
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Acyl-Carrier Protein S-Malonyltransferase / genetics
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Acyl-Carrier Protein S-Malonyltransferase / metabolism
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Amino Acid Sequence
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Catalytic Domain / genetics
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Crystallography, X-Ray
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Drug Design*
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Enzyme Assays
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Enzyme Inhibitors / chemical synthesis*
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / genetics
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Protein Conformation
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Sequence Homology, Amino Acid
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Staphylococcus aureus / enzymology
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Staphylococcus aureus / genetics
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Streptococcus pneumoniae / enzymology
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Streptococcus pneumoniae / genetics
Substances
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Enzyme Inhibitors
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Acyl-Carrier Protein S-Malonyltransferase