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PDBsum entry 4g0c
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Lyase/lyase inhibitor
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PDB id
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4g0c
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References listed in PDB file
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Key reference
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Title
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Neutron diffraction of acetazolamide-Bound human carbonic anhydrase ii reveals atomic details of drug binding.
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Authors
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S.Z.Fisher,
M.Aggarwal,
A.Y.Kovalevsky,
D.N.Silverman,
R.Mckenna.
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Ref.
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J Am Chem Soc, 2012,
134,
14726-14729.
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PubMed id
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Abstract
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Carbonic anhydrases (CAs) catalyze the hydration of CO(2) forming HCO(3)(-) and
a proton, an important reaction for many physiological processes including
respiration, fluid secretion, and pH regulation. As such, CA isoforms are
prominent clinical targets for treating various diseases. The clinically used
acetazolamide (AZM) is a sulfonamide that binds with high affinity to human CA
isoform II (HCA II). There are several X-ray structures available of AZM bound
to various CA isoforms, but these complexes do not show the charged state of AZM
or the hydrogen atom positions of the protein and solvent. Neutron diffraction
is a useful technique for directly observing H atoms and the mapping of
H-bonding networks that can greatly contribute to rational drug design. To this
end, the neutron structure of H/D exchanged HCA II crystals in complex with AZM
was determined. The structure reveals the molecular details of AZM binding and
the charged state of the bound drug. This represents the first determined
neutron structure of a clinically used drug bound to its target.
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