3S8X

Crystal structure of human carbonic anhydrase isozyme II with 4-{[(4-methyl-6-oxo-1,6-dihydro-2-pyrimidinyl)sulfanyl]acetyl}benzenesulfonamide

3S8X の概要

• エントリーDOI: 10.2210/pdb3s8x/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, DIMETHYL SULFOXIDE, ... (6 entities in total)
• 機能のキーワード: drug design, carbonic anhydrase, sulfonamide, metal-binding, 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: 30013.30

構造登録者

Grazulis, S.,Manakova, E.,Tamulaitiene, G. (登録日: 2011-05-31, 公開日: 2012-04-11, 最終更新日: 2023-09-13)

主引用文献

Capkauskaite, E.,Zubriene, A.,Baranauskiene, L.,Tamulaitiene, G.,Manakova, E.,Kairys, V.,Grazulis, S.,Tumkevicius, S.,Matulis, D.
Design of [(2-pyrimidinylthio)acetyl]benzenesulfonamides as inhibitors of human carbonic anhydrases.
Eur.J.Med.Chem., 51:259-270, 2012

PubMed Abstract: A series of [(2-pyrimidinylthio)acetyl]benzenesulfonamides were designed and synthesized. Their binding affinities as inhibitors of several recombinant human carbonic anhydrase (CA) isozymes were determined by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). A group of compounds containing a chlorine atom in the benzenesulfonamide ring were found to exhibit higher selectivity but lower binding affinity toward tested CAs. The crystal structures of selected compounds in complex with CA II were determined to atomic resolution. Docking studies were performed to compare the binding modes of experimentally determined crystallographic structures with computational prediction of the pyrimidine derivative binding to CA II. Several compounds bound to select CAs with single-digit nanomolar affinities and could be used as leads for inhibitor development toward a select CA isozyme.

PubMed: 22440859
DOI: 10.1016/j.ejmech.2012.02.050

実験手法

X-RAY DIFFRACTION (1.3 Å)