6B4D

Crystal structure of human carbonic anhydrase II in complex with a heteroaryl-pyrazole carboxylic acid derivative.

「5CJL」から置き換えられました

6B4D の概要

• エントリーDOI: 10.2210/pdb6b4d/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, DIMETHYL SULFOXIDE, ... (6 entities in total)
• 機能のキーワード: carbonic anhydrase, inhibitor, carboxylic acid, lyase
• 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: 29515.71

構造登録者

Lomelino, C.L.,Mahon, B.P.,McKenna, R. (登録日: 2017-09-26, 公開日: 2018-02-07, 最終更新日: 2023-10-04)

主引用文献

Cadoni, R.,Pala, N.,Lomelino, C.,Mahon, B.P.,McKenna, R.,Dallocchio, R.,Dessi, A.,Carcelli, M.,Rogolino, D.,Sanna, V.,Rassu, M.,Iaccarino, C.,Vullo, D.,Supuran, C.T.,Sechi, M.
Exploring Heteroaryl-pyrazole Carboxylic Acids as Human Carbonic Anhydrase XII Inhibitors.
ACS Med Chem Lett, 8:941-946, 2017

PubMed Abstract: We report the synthesis, biological evaluation, and structural study of a series of substituted heteroaryl-pyrazole carboxylic acid derivatives. These compounds have been developed as inhibitors of specific isoforms of carbonic anhydrase (CA), with potential as prototypes of a new class of chemotherapeutics. Both X-ray crystallography and computational modeling provide insights into the CA inhibition mechanism. Results indicate that this chemotype produces an indirect interference with the zinc ion, thus behaving differently from other related nonclassical inhibitors. Among the tested compounds, with = 0.21 μM toward CA XII demonstrated significant antiproliferative activity against hypoxic tumor cell lines. Taken together, the results thus provide the basis of structural determinants for the development of novel anticancer agents.

PubMed: 28947941
DOI: 10.1021/acsmedchemlett.7b00229

実験手法

X-RAY DIFFRACTION (1.196 Å)