Editors' ChoiceBiochemistry

Novel Redox Intermediates

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Science's STKE  17 Jun 2003:
Vol. 2003, Issue 187, pp. tw231-TW231
DOI: 10.1126/stke.2003.187.tw231

Understanding how oxidation of proteins leads to reversible alterations in protein function is relevant for proteins involved in cellular signaling processes, including protein tyrosine phosphatases (PTPs). Two groups, Salmeen et al. and van Montfort et al., show that PTP1B is reversibly oxidized by such chemicals as hydrogen peroxide or 2-phenyl-isoxazalidine-3,5-dione and forms a previously uncharacterized sulfenyl-amide because of oxidation of the catalytic site cysteine. Both groups analyzed the crystal structure of PTP1B after exposure to oxidizing conditions and identified the formation of the sulfenyl-amide, which caused large changes in the conformation of the active site. Salmeen et al. reported inhibition of substrate binding in the peroxide-exposed PTP1B, consistent with the structural changes blocking substrate recognition. This novel intermediate may effectively protect PTP1B from irreversible inactivation that would result from the formation of sulfinic or sulfonic acids.

A. Salmeen, J. N. Andersen, M. P. Myers, T.-C. Meng, J. A. Hinks, N. K. Tonks, D. Barford, Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423, 769-773 (2003). [Online Journal]

R. L. M. van Montfort, M. Congreve, D. Tisi, R. Carr, H. Jhoti, Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature 423, 773-777 (2003). [Online Journal]