4G0C
Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding.
Summary for 4G0C
| Entry DOI | 10.2210/pdb4g0c/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE, ... (4 entities in total) |
| Functional Keywords | carbonic anhydrase, acetazolamide, hydrogen bonding, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm : P00918 |
| Total number of polymer chains | 1 |
| Total formula weight | 29220.29 |
| Authors | Fisher, S.Z.,McKenna, R.,Aggarwal, M. (deposition date: 2012-07-09, release date: 2012-09-19, Last modification date: 2023-09-13) |
| Primary citation | Fisher, S.Z.,Aggarwal, M.,Kovalevsky, A.Y.,Silverman, D.N.,McKenna, R. Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding. J.Am.Chem.Soc., 134:14726-14729, 2012 Cited by PubMed Abstract: 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. PubMed: 22928733DOI: 10.1021/ja3068098 PDB entries with the same primary citation |
| Experimental method | NEUTRON DIFFRACTION (2 Å) |
Structure validation
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