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Letter

Structure of Human Cytidine Deaminase Bound to a Potent Inhibitor

Supporting Info

Sang J. Chung,^†^§ J. Christopher Fromme,^‡ and Gregory L. Verdine*^†^‡

Department of Chemistry and Chemical Biology, and Department of Molecular and Cellular Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138

J. Med. Chem., 2005, 48 (3), pp 658–660

DOI: 10.1021/jm0496279

Publication Date (Web): January 7, 2005

†

Department of Chemistry and Chemical Biology.

Present address: Korea Research Institute of Bioscience & Biotechnology 52 Eoeun-dong, Yuseong-gu, Daejeon, 305-333 Korea.

‡

Department of Molecular and Cellular Biology.

To whom correspondence should be addressed. Phone: 1-617-495-5323. Fax: 1-617-495-8755. E-mail: verdine@chemistry.harvard.edu.

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 π/π-interaction with a key active site residue, Phe 137.

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Published In Issue February 10, 2005
Received May 20, 2004

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Letter

Structure of Human Cytidine Deaminase Bound to a Potent Inhibitor