Is the geometry of Vanadium in active site of phosphatases
important for inhibitor design and antidiabetic properties of
vanadium compounds
D. C. Crans
Department of Chemistry, Colorado State University, Fort Collins,CO ,USA
e-mail: Debbie.Crans@ColoState.edu
Vanadate, and vanadium compounds are insulin enhancing agents and
representative compounds have been tested in animal systems and human beings.1-3
The specific mode of action and the active species have remained elusive such studies
being complicated by the complex speciation. One mode of action of these
compounds is believed to be inhibition of phosphatases.1-7 In the following
presentation we will investigate the structural aspects of oxovanadate and vanadium
complexes coordinated to phosphatases. Specifically, we examine the active sites of
the 29 known X-ray structures and analyze the coordination chemistry of the
vanadium atoms in the active site and characterize them with regard to trigonal
bipyramidal or square pyramidal character. We also compare these systems with
small molecule vanadium complexes to determine if the forms in the protein complex
is similar to the small molecules characterized.8-10 These considerations demonstrate
that a trigonal bipyramidal geometry is observed in the vanadium-phosphatase
complexes even though the square pyramidal geometry is more stable for the
complexes themselves. These observations were compared to the biochemical data
available measuring Ki values for oxovanadates as well as other oxometalates and
finally for vanadium compounds.9 We also use the data-mining and shape analysis to
investigate the nature of the inhibition by mechanistic investigation of the hydrolysis
of the PTP1B reaction surface. Together all these data are used to provide direction
with regard to inhibitor design.
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8. D.C. Crans, M.L. Tarlton, C.C. McLauchlan, Eur. J. Inorg. Chem., In press (2014).
9. C. C. McLauchlan, B. J. Peters, G. R. Willsky and D. C. Crans, Coord. Chem. Rev. 2015; ASAP,
http://dx.doi.org/10.1016/j.ccr.2014.12.012
10. I. Sanchez-Lombardo, S. Alvarez, C. C. McLauchlan, and Debbie C. Crans J. Inorg. Chem. 2015,
under revision.
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