4KNN

Crystal structure of human carbonic anhydrase isozyme XIII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide

4KNN の概要

• エントリーDOI: 10.2210/pdb4knn/pdb
• 関連するPDBエントリー: 4KNI 4KNJ 4KNM 4KP5 4KP8
• 分子名称: Carbonic anhydrase 13, ZINC ION, 2-chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide, ... (8 entities in total)
• 機能のキーワード: drug design, carbonic anhydrase, benzenesulfonamide, metal-binding, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60901.80

構造登録者

Smirnov, A.,Manakova, E.,Grazulis, S. (登録日: 2013-05-10, 公開日: 2013-11-06, 最終更新日: 2023-11-08)

主引用文献

Capkauskaite, E.,Zubriene, A.,Smirnov, A.,Torresan, J.,Kisonaite, M.,Kazokaite, J.,Gylyte, J.,Michailoviene, V.,Jogaite, V.,Manakova, E.,Grazulis, S.,Tumkevicius, S.,Matulis, D.
Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII
Bioorg.Med.Chem., 21:6937-6947, 2013

PubMed Abstract: Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5 nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms.

PubMed: 24103428
DOI: 10.1016/j.bmc.2013.09.029

実験手法

X-RAY DIFFRACTION (1.404 Å)