8ROW

Human Carbonic Anhydrase II in complex with biguanide derivative inhibitor 1-carbamimidamido-N-[(4 sulfamoylphenyl)methyl]methanimidamide, using glycerol as cryoprotectant

これはPDB形式変換不可エントリーです。

8ROW の概要

• エントリーDOI: 10.2210/pdb8row/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 1-carbamimidoyl-3-[(4-sulfamoylphenyl)methyl]guanidine, ... (5 entities in total)
• 機能のキーワード: metalloenzyme, lyase, inhibitor
• 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: 29987.19

構造登録者

Baroni, C.,Ferraroni, M. (登録日: 2024-01-12, 公開日: 2025-01-29, 最終更新日: 2026-02-11)

主引用文献

Baroni, C.,Bozdag, M.,Renzi, G.,De Luca, V.,Capasso, C.,Bazzicalupi, C.,Selleri, S.,Ferraroni, M.,Carta, F.,Supuran, C.T.
X-ray crystallographic and kinetic studies of biguanide containing aryl sulfonamides as carbonic anhydrase inhibitors.
Rsc Med Chem, 16:1633-1640, 2025

PubMed Abstract: Here, we report a small series of dual-targeting compounds that combine the prototypical carbonic anhydrase (CA) zinc-binding sulfonamide moiety with the biguanide group of metformin, an emerging anticancer drug. The compounds reported similar inhibition profiles on a panel of physiologically relevant human (h)CAs, with marked selectivity for the cancer related IX and XII isoforms. The binding modes of representative inhibitors 5b and 5c within the active site of the hCA isoforms II and XII-mimic were assessed by X-ray crystallography, thus allowing us to clarify molecular features that may be useful for the design of more specific and potent inhibitors. For instance, we identified a mutation in the hCA XII-mimic which was found responsible for the selectivity of the ligands toward the tumor associated isoform. Interestingly, in the hCA II/5c complex, a second inhibitor molecule was bound to the catalytic cleft, probably affecting the inhibition properties of the canonical zinc-bound inhibitor.

PubMed: 39935522
DOI: 10.1039/d4md01018c

実験手法

X-RAY DIFFRACTION (1.05 Å)