Metavanadate at the Active Site of the Phosphatase VHZ

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• 作者：Vyacheslav I. Kuznetsov ; Anastassia N. Alexandrova ; Alvan C. Hengge
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：September 5, 2012
• 年：2012
• 卷：134
• 期：35
• 页码：14298-14301
• 全文大小：247K
• 年卷期：v.134,no.35(September 5, 2012)
• ISSN：1520-5126

文摘

Vanadate is a potent modulator of a number of biological processes and has been shown by crystal structures and NMR spectroscopy to interact with numerous enzymes. Although these effects often occur under conditions where oligomeric forms dominate, the crystal structures and NMR data suggest that the inhibitory form is usually monomeric orthovanadate, a particularly good inhibitor of phosphatases because of its ability to form stable trigonal-bipyramidal complexes. We performed a computational analysis of a 1.14 脜 structure of the phosphatase VHZ in complex with an unusual metavanadate species and compared it with two classical trigonal-bipyramidal vanadate鈥損hosphatase complexes. The results support extensive delocalized bonding to the apical ligands in the classical structures. In contrast, in the VHZ metavanadate complex, the central, planar VO₃^{鈥?/sup> moiety has only one apical ligand, the nucleophilic Cys95, and a gap in electron density between V and S. A computational analysis showed that the V鈥揝 interaction is primarily ionic. A mechanism is proposed to explain the formation of metavanadate in the active site from a dimeric vanadate species that previous crystallographic evidence has shown to be able to bind to the active sites of phosphatases related to VHZ. Together, the results show that the interaction of vanadate with biological systems is not solely reliant upon the prior formation of a particular inhibitory form in solution. The catalytic properties of an enzyme may act upon the oligomeric forms primarily present in solution to generate species such as the metavanadate ion observed in the VHZ structure.}