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PDBsum entry 3h2c
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Transferase/transferase inhibitor
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PDB id
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3h2c
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References listed in PDB file
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Key reference
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Title
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Structural studies of pterin-Based inhibitors of dihydropteroate synthase.
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Authors
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K.E.Hevener,
M.K.Yun,
J.Qi,
I.D.Kerr,
K.Babaoglu,
J.G.Hurdle,
K.Balakrishna,
S.W.White,
R.E.Lee.
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Ref.
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J Med Chem, 2010,
53,
166-177.
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PubMed id
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Abstract
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Dihydropteroate synthase (DHPS) is a key enzyme in bacterial folate synthesis
and the target of the sulfonamide class of antibacterials. Resistance and
toxicities associated with sulfonamides have led to a decrease in their clinical
use. Compounds that bind to the pterin binding site of DHPS, as opposed to the
p-amino benzoic acid (pABA) binding site targeted by the sulfonamide agents, are
anticipated to bypass sulfonamide resistance. To identify such inhibitors and
map the pterin binding pocket, we have performed virtual screening, synthetic,
and structural studies using Bacillus anthracis DHPS. Several compounds with
inhibitory activity have been identified, and crystal structures have been
determined that show how the compounds engage the pterin site. The structural
studies identify the key binding elements and have been used to generate a
structure-activity based pharmacophore map that will facilitate the development
of the next generation of DHPS inhibitors which specifically target the pterin
site.
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