Structural basis for the rational design of new anti-Brucella agents: The crystal structure of the C366S mutant of l-histidinol dehydrogenase from Brucella suis
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- 作者：Katia D'ambrosio ; Marie Lopez ; Nina A. Dathan ; Safia Ouahrani-Bettache ; Stephan K枚hler ; Giuseppina Ascione ; Simona Maria Monti ; Jean-Yves Winum ; Giuseppina De Simone
- 关键词：X-ray crystallography ; Drug design ; l-Histidinol dehydrogenase ; Brucella suis ; Inhibitor
- 刊名：Biochimie
- 出版年：February, 2014
- 年：2014
- 卷：97
- 期：Complete
- 页码：114-120
- 全文大小：2172 K
文摘
l-Histidinol dehydrogenase from Brucella suis (BsHDH) is an enzyme involved in the histidine biosynthesis pathway which is absent in mammals, thus representing a very interesting target for the development of anti-Brucella agents. In this paper we report the crystallographic structure of a mutated form of BsHDH both in its unbound form and in complex with a nanomolar inhibitor. These studies provide the first structural background for the rational design of potent HDH inhibitors, thus offering new hints for clinical applications.