5E2R

The crystal structure of the human carbonic anhydrase II in complex with a 1,1'-biphenyl-4-sulfonamide inhibitor

5E2R の概要

• エントリーDOI: 10.2210/pdb5e2r/pdb
• 関連するPDBエントリー: 5CJF
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4'-(4-aminobenzoyl)biphenyl-4-sulfonamide, ... (5 entities in total)
• 機能のキーワード: 1'-biphenyl-4-sulfonamide, lyase, complex, 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: 29987.22

構造登録者

Alterio, V.,De Simone, G. (登録日: 2015-10-01, 公開日: 2015-11-04, 最終更新日: 2024-01-10)

主引用文献

La Regina, G.,Coluccia, A.,Famiglini, V.,Pelliccia, S.,Monti, L.,Vullo, D.,Nuti, E.,Alterio, V.,De Simone, G.,Monti, S.M.,Pan, P.,Parkkila, S.,Supuran, C.T.,Rossello, A.,Silvestri, R.
Discovery of 1,1'-Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors.
J.Med.Chem., 58:8564-8572, 2015

PubMed Abstract: New 1,1'-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1-21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1'-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.

PubMed: 26497049
DOI: 10.1021/acs.jmedchem.5b01144

実験手法

X-RAY DIFFRACTION (1.6 Å)