Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na2[VO(Glu)2(CH3OH)](Glu = glutamate).
The insulin-sensitizing effect of vanadium complexes has been linked to their ability to inhibit protein tyrosine phosphatases (PTPs). Considering that vanadium complexes may exchange in vivo with amino acids, forming in situ vanadium-amino acid complexes, we have synthesized and characterized an oxovanadium glutamate complex, Na(2)[V(IV)O(Glu)(2)(CH(3)OH)]H(2)O (1·H(2)O). The complex showed potent inhibition against four human PTPs (PTP1B, TCPTP, HePTP, and SHP-1) with IC(50) in the 0.21-0.37 μM ranges. Fluorescence titration studies suggest that the complex binds to PTP1B with the formation of a 2:1 complex. Enzyme kinetics analysis using Lineweaver-Burk plots indicates a typical competitive inhibition mode.
Lu
Liping
L
Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan, 030006, Shanxi, People's Republic of China.
Wang
Sulian
S
Zhu
Miaoli
M
Liu
Zhiwei
Z
Guo
Maolin
M
Xing
Shu
S
Fu
Xueqi
X
D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D005971:Glutamates / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014638:Vanadates / Q000494:pharmacology*
D056831:Coordination Complexes; D005971:Glutamates; D014638:Vanadates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases