Crystal Structures of Phosphite Dehydrogenase Provide Insights into Nicotinamide Cofactor Regeneration

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• 作者：Yaozhong Zou ; Houjin Zhang ; Joseph S. Brunzelle ; Tyler W. Johannes ; Ryan Woodyer ; John E. Hung ; Nikhil Nair ; Wilfred A. van der Donk ; Huimin Zhao ; Satish K. Nair
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：May 29, 2012
• 年：2012
• 卷：51
• 期：21
• 页码：4263-4270
• 全文大小：393K
• 年卷期：v.51,no.21(May 29, 2012)
• ISSN：1520-4995

文摘

The enzyme phosphite dehydrogenase (PTDH) catalyzes the NAD⁺-dependent conversion of phosphite to phosphate and represents the first biological catalyst that has been shown to conduct the enzymatic oxidation of phosphorus. Despite investigation for more than a decade into both the mechanism of its unusual reaction and its utility in cofactor regeneration, there has been a lack of any structural data for PTDH. Here we present the cocrystal structure of an engineered thermostable variant of PTDH bound to NAD⁺ (1.7 脜 resolution), as well as four other cocrystal structures of thermostable PTDH and its variants with different ligands (all between 1.85 and 2.3 脜 resolution). These structures provide a molecular framework for understanding prior mutational analysis and point to additional residues, located in the active site, that may contribute to the enzymatic activity of this highly unusual catalyst.