3KWA

Polyamines inhibit carbonic anhydrases

3KWA の概要

• エントリーDOI: 10.2210/pdb3kwa/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• 機能のキーワード: polyamines, carbonic anhydrase ii, inhibition, 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: 29757.40

構造登録者

Temperini, C. (登録日: 2009-12-01, 公開日: 2010-07-14, 最終更新日: 2023-11-01)

主引用文献

Carta, F.,Temperini, C.,Innocenti, A.,Scozzafava, A.,Kaila, K.,Supuran, C.T.
Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule
J.Med.Chem., 53:5511-5522, 2010

PubMed Abstract: Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, phenols, and coumarins. Polyamines such as spermine, spermidine, and many synthetic congeners are described to constitute a novel class of CA inhibitors (CAIs), interacting with the different CA isozymes with efficiency from the low nanomolar to millimolar range. The main structure-activity relationship for these CAIs have been delineated: the length of the molecule, number of amine moieties, and their functionalization are the main parameters controlling activity. The X-ray crystal structure of the CA II-spermine adduct allowed understanding of the inhibition mechanism. Spermine anchors to the nonprotein zinc ligand through a network of hydrogen bonds. Its distal amine moiety makes hydrogen bonds with residues Thr200 and Pro201, which further stabilize the adduct. Spermine binds differently compared to sulfonamides, phenols, or coumarins, rendering possible to develop CAIs with a diverse inhibition mechanism, profile, and selectivity for various isoforms.

PubMed: 20590092
DOI: 10.1021/jm1003667

実験手法

X-RAY DIFFRACTION (2 Å)