与一种强效抑制剂结合的人胞苷脱氨酶的结构

Structure of human cytidine deaminase bound to a potent inhibitor.

作者信息

Chung Sang J, Fromme J Christopher, Verdine Gregory L

机构信息

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.

出版信息

J Med Chem. 2005 Feb 10;48(3):658-60. doi: 10.1021/jm0496279.

DOI:10.1021/jm0496279

PMID:15689149

Abstract

Human cytidine deaminase (CDA) is an enzyme prominent for its role in catalyzing metabolic processing of nucleoside-type anticancer and antiviral agents. It is thus a promising target for the development of small molecule therapeutic adjuvants. We report the first crystal structure of human CDA as a complex with a tight-binding inhibitor, diazepinone riboside 1. The structure reveals that inhibitor 1 is able to establish a canonical pi/pi-interaction with a key active site residue, Phe 137.

摘要

人胞苷脱氨酶（CDA）是一种因其在催化核苷型抗癌和抗病毒药物的代谢过程中所起的作用而备受瞩目的酶。因此，它是开发小分子治疗佐剂的一个有前景的靶点。我们报道了人CDA与紧密结合抑制剂二氮杂卓酮核糖苷1形成复合物的首个晶体结构。该结构表明抑制剂1能够与关键活性位点残基苯丙氨酸137建立典型的π/π相互作用。