tailieunhanh - Báo cáo khoa học: Different modes of dipeptidyl peptidase IV (CD26) inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites

Dipeptidyl peptidase IV (DP IV, CD26) plays an essential role in the activation and proliferation of lymphocytes, which is shown by the immunosuppressive effects of syn-thetic DP IV inhibitors. Similarly, both human immuno-deficiency virus-1 (HIV-1) Tat protein and the N-terminal peptide Tat(1–9) inhibit DP IV activity and T cell prolifer-ation. Therefore, the N-terminal amino acid sequence of HIV-1 Tat is important for the inhibition of DP IV. | Eur. J. Biochem. 270 2147-2156 2003 FEBS 2003 doi Different modes of dipeptidyl peptidase IV CD26 inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites Susan Lorev1. Angela Stockel-Maschek1. Jiiraen Faust1 Wolfaana Brandt2 Beate Stiebitz1. Mark D. Gorrell3 Thilo Kahne4 Carmen Mrestani-Klaus1 Sabine Wrenger5 Dirk Reinhold5 Siegfried Ansorge6 and Klaus Neubert1 1 Department of BiochemistryịBiotechnology Institute of Biochemistry Martin-Luther-University Halle-Wittenberg Halle Germany 2 Institute of Plant Biochemistry Leibniz Institute Halle Germany 3 AW Morrow Gastroenterology and Liver Center Royal Prince Alfred Hospital Newtown NSW Australia 4Department of Internal Medicine Institute of Experimental Internal Medicine and 5Institute of Immunology Otto-von-Guericke-University Magdeburg Germany 6IMTM Magdeburg Germany Dipeptidyl peptidase IV DP IV CD26 plays an essential role in the activation and proliferation of lymphocytes which is shown by the immunosuppressive effects of synthetic DP IV inhibitors. Similarly both human immunodeficiency virus-1 HIV-1 Tat protein and the N-terminal peptide Tat 1-9 inhibit DP IV activity and T cell proliferation. Therefore the N-terminal amino acid sequence of HIV-1 Tat is important for the inhibition of DP IV. Recently we characterized the thromboxane A2 receptor peptide TXA2-R 1-9 bearing the N-terminal MWP sequence motif as a potent DP IV inhibitor possibly playing a functional role during antigen presentation by inhibiting T cell-expressed DP IV Wrenger S. Faust J. Mrestani-Klaus C. Fengler A. Stockel-Maschek A. Lorey S. Kahne T. Brandt W. Neubert K. Ansorge S. Reinhold D. 2000 J. Biol. Chem. 275 22180-22186 . Here we demonstrate that amino acid substitutions at different positions of Tat 1-9 can result in a change of the inhibition type. Certain Tat 1-9 -related peptides are found to be competitive and others linear mixed-type or .