6FJI

Joint neutron and x-ray crystal structure of human carbonic anhydrase IX mimic (apo).

6FJI の概要

• エントリーDOI: 10.2210/pdb6fji/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION (3 entities in total)
• 機能のキーワード: joint x-ray neutron diffraction, carbonic anhydrase, 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: 29266.30

構造登録者

Fisher, S.Z. (登録日: 2018-01-22, 公開日: 2019-02-06, 最終更新日: 2024-05-01)

主引用文献

Koruza, K.,Mahon, B.P.,Blakeley, M.P.,Ostermann, A.,Schrader, T.E.,McKenna, R.,Knecht, W.,Fisher, S.Z.
Using neutron crystallography to elucidate the basis of selective inhibition of carbonic anhydrase by saccharin and a derivative.
J. Struct. Biol., 205:147-154, 2019

PubMed Abstract: Up-regulation of carbonic anhydrase IX (CA IX) expression is an indicator of metastasis and associated with poor cancer patient prognosis. CA IX has emerged as a cancer drug target but development of isoform-specific inhibitors is challenging due to other highly conserved CA isoforms. In this study, a CA IX construct was used (CA II with seven point mutations introduced, to mimic CA IX active site) while maintaining CA II solubility that make it amenable to crystallography. The structures of CA IX unbound and in complex with saccharin (SAC) and a saccharin-glucose conjugate (SGC) were determined using joint X-ray and neutron protein crystallography. Previously, SAC and SGC have been shown to display CA isoform inhibitor selectivity in assays and X-ray crystal structures failed to reveal the basis of this selectivity. Joint X-ray and neutron crystallographic studies have shown active site residues, solvent, and H-bonding re-organization upon SAC and SGC binding. These observations highlighted the importance of residues 67 (Asn in CA II, Gln in CA IX) and 130 (Asp in CA II, Arg in CA IX) in selective CA inhibitor targeting.

PubMed: 30639924
DOI: 10.1016/j.jsb.2018.12.009

実験手法

NEUTRON DIFFRACTION (2.033 Å)
X-RAY DIFFRACTION (1.6 Å)