The essential role of a free sulfhydryl group in blocking the cholesteryl site of cholesteryl ester transfer protein (CETP)

Chemistry and Physics of Lipids
Dennis E Epps, Anne F Vosters

Abstract

Cholesteryl ester transfer protein (CETP) has at least one unpaired sulfhydryl residue, which we have shown previously to be in or near the active site region. We investigated the location of this unpaired cysteine residue(s) of CETP using chemical modification with fluorescent sulfhydryl-specific reagents, limited proteolysis, and amino acid/sequence analysis. The kinetics of labeling CETP by either 2-(4'-maleimidylanilino)-naphthalene-6-sulfonic acid (MIANS) or acrylodan were followed by observing the increase in fluorescence of the bound probes. Labeling was inhibited strongly by preincubation of the CETP with either PNU-617, a competitive inhibitor of cholesteryl ester (CE) transport, and TP2 antibody. In addition, the transfer activities of the substrate CE by the modified CETP's were also inhibited but not competitively. Finally, preincubation of the native protein with N-ethylmaleimide (NEM) resulted in inhibition of activity that was dependent upon the time of exposure of the protein to the alkylating agent. These results provide further evidence that there is a cysteine residue in the active site region of CETP and ligands that either react or bind to this residue produce steric hindrance to CE transfer activity. Final...Continue Reading

References

Dec 17, 1975·Biochimica Et Biophysica Acta·D B ZilversmitJ Balmer
Jun 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·K R MarottiG W Melchior
Jun 5, 1996·Biochemical and Biophysical Research Communications·D T ConnollyK Glenn

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Citations

Dec 9, 2010·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·P M CazitaE C R Quintão
Mar 19, 2003·Current Opinion in Lipidology·Andreas Ritsch, Josef R Patsch
May 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Chungyu ChangHung Ton-That
Nov 19, 2019·Frontiers in Chemistry·Gaspar P PintoJiri Damborsky

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