Gold(I) phosphine mediated selective inhibition of lymphoid tyrosine phosphatase

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Author list: Karver MR, Krishnamurthy D, Bottini N, Barrios AM
Publisher: Elsevier
Publication year: 2010
Journal: Journal of Inorganic Biochemistry (0162-0134)
Volume number: 104
Issue number: 3
Start page: 268
End page: 273
Number of pages: 6
ISSN: 0162-0134
Languages: English-Great Britain (EN-GB)


Abstract

Selective protein tyrosine phosphatase (PTP) inhibition is often difficult to achieve owing to the high degree of similarity of the catalytic domains of this family of enzymes. Selective inhibitors of the lymphoid specific tyrosine phosphatase, LYP, are of great interest due to the involvement of LYP in several autoimmune disorders. This manuscript describes a study into the mechanistic details of selective LYP inhibition by a Au(1)-phosphine complex. The complex, [Au((CH(2)CH(2)CN)(2)PPh)Cl], selectively inhibits LYP activity both in vitro and in cells, but does not inhibit other T-cell derived PTPs including the highly homologous PTP-PEST. The mode of inhibition was probed by investigating inhibition of LYP, the LYP mutant C129/231 S, and PTP-PEST. Inhibition of LYP and PTP-PEST was competitive, while the LYP double mutant appeared mixed. Wild-type LYP was inhibited more potently than LYP C129/231S, indicating an important role for at least one of these residues in Au(I) binding. Coordination of Au(I) by both the active site cysteine residue as well as either Cys129 or 231 is suggested as a potential mechanism for LYP selective inhibition. (C) 2009 Elsevier Inc. All rights reserved.


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Last updated on 2019-23-08 at 11:15