Abstract
The binding of FtsZ to ZipA is a potential target for antibacterial therapy. Based on a small molecule inhibitor of the ZipA-FtsZ interaction, a parallel synthesis of small molecules was initiated which targeted a key region of ZipA involved in FtsZ binding. The X-ray crystal structure of one of these molecules complexed with ZipA was solved. The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water.
MeSH terms
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Amino Acid Sequence
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Carrier Proteins / antagonists & inhibitors*
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / metabolism*
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Drug Design*
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Escherichia coli Proteins / antagonists & inhibitors*
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Escherichia coli Proteins / metabolism*
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / metabolism
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Molecular Sequence Data
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Protein Binding / physiology
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / metabolism
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Escherichia coli Proteins
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FtsZ84 protein, E coli
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Indoles
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Quinazolines
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ZipA protein, E coli
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indolo(2,1-b)quinazoline