Dioxygen, an unexpected carbonic anhydrase ligand

Journal of Enzyme Inhibition and Medicinal Chemistry

Claudiu T. Supuran¹  Marta Ferraroni²  Andrea Scozzafava²  Andrea Cavalli³  Roberto Gaspari⁴ 

[1] Dipartimento NEUROFARBA – Pharmaceutical and Nutraceutical Section, Sesto Fiorentino (FI), Itali;Dipartimento di Chimica, Università di Firenze, Sesto Fiorentino (FI), Italia;Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Bologna, Italia;Istituto Italiano di Tecnologia, Genova, Italia;

关键词: Carbonic anhydrase;    oxygen;    crystallography;    molecular dynamics;   

DOI  :  10.1080/14756366.2018.1475371

来源: publisher

【 摘 要 】

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, grouped into seven different classes, which catalyze the reaction of CO2 hydration to bicarbonate and protons. All of the fifteen human isoforms reported to date belong to the α-class and contain zinc as a cofactor. The structure of human Zn,Cu-CA II has been solved which contains a copper ion bound at its N-terminal, coordinated to His4 and His64. In the active site a dioxygen molecule is coordinated to the zinc ion. Since dioxygen is a rather unexpected CA ligand, molecular dynamics (MD) simulations were performed which suggested a superoxide character of the zinc bound O2.

【 授权许可】

CC BY