4G0C

Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding.

4G0C の概要

• エントリーDOI: 10.2210/pdb4g0c/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE, ... (4 entities in total)
• 機能のキーワード: carbonic anhydrase, acetazolamide, hydrogen bonding, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29220.29

構造登録者

Fisher, S.Z.,McKenna, R.,Aggarwal, M. (登録日: 2012-07-09, 公開日: 2012-09-19, 最終更新日: 2023-09-13)

主引用文献

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

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: 22928733
DOI: 10.1021/ja3068098

実験手法

NEUTRON DIFFRACTION (2 Å)