6Z04

Nido-carborane butyl-sulfonamide in complex with CA IX mimic

6Z04 の概要

• エントリーDOI: 10.2210/pdb6z04/pdb
• 関連するPDBエントリー: 6YZJ 6YZK 6YZL 6YZM 6YZN 6YZO 6YZP 6YZQ 6YZR 6YZS 6YZT 6YZU 6YZV 6YZW 6YZX
• 分子名称: Carbonic anhydrase 2, ZINC ION, Carborane nido-butyl-sulfonamide, ... (4 entities in total)
• 機能のキーワード: carbonic anhydrase, ca inhibitor, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29523.81

構造登録者

Kugler, M.,Brynda, J.,Pospisilova, K.,Rezacova, P. (登録日: 2020-05-07, 公開日: 2020-10-28, 最終更新日: 2024-01-24)

主引用文献

Kugler, M.,Holub, J.,Brynda, J.,Pospisilova, K.,Anwar, S.E.,Bavol, D.,Havranek, M.,Kral, V.,Fabry, M.,Gruner, B.,Rezacova, P.
The structural basis for the selectivity of sulfonamido dicarbaboranes toward cancer-associated carbonic anhydrase IX.
J Enzyme Inhib Med Chem, 35:1800-1810, 2020

PubMed Abstract: Human carbonic anhydrase IX (CA IX), a protein specifically expressed on the surface of solid tumour cells, represents a validated target both for anticancer therapy and diagnostics. We recently identified sulfonamide dicarbaboranes as promising inhibitors of CA IX with favourable activities both and . To explain their selectivity and potency, we performed detailed X-ray structural analysis of their interactions within the active sites of CA IX and CA II. Series of compounds bearing various aliphatic linkers between the dicarbaborane cluster and sulfonamide group were examined. Preferential binding towards the hydrophobic part of the active site cavity was observed. Selectivity towards CA IX lies in the shape complementarity of the dicarbaborane cluster with a specific CA IX hydrophobic patch containing V131 residue. The bulky side chain of F131 residue in CA II alters the shape of the catalytic cavity, disrupting favourable interactions of the spherical dicarbaborane cluster.

PubMed: 32962427
DOI: 10.1080/14756366.2020.1816996

実験手法

X-RAY DIFFRACTION (1.05 Å)