2bgr: Difference between revisions
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==Overview== | ==Overview== | ||
CD26 or dipeptidyl-peptidase IV (DPPIV) is engaged in immune functions by, co-stimulatory effects on activation and proliferation of T lymphocytes, binding to adenosine deaminase, and regulation of various chemokines and, cytokines. DPPIV peptidase activity is inhibited by both Tat protein from, human immunodeficiency virus (HIV)-1 and its N-terminal nonapeptide, Tat-(1-9) with amino acid sequence MDPVDPNIE, suggesting that DPPIV, mediates immunosuppressive effects of Tat protein. The 2.0- and 3.15-A, resolution crystal structures of the binary complex between human DPPIV, and nonapeptide Tat-(1-9) and the ternary complex between the variant, MWPVDPNIE, called Trp(2)-Tat-(1-9), and DPPIV bound to adenosine deaminase, show that Tat-(1-9) and Trp(2)-Tat-(1-9) are located in the active site .. | CD26 or dipeptidyl-peptidase IV (DPPIV) is engaged in immune functions by, co-stimulatory effects on activation and proliferation of T lymphocytes, binding to adenosine deaminase, and regulation of various chemokines and, cytokines. DPPIV peptidase activity is inhibited by both Tat protein from, human immunodeficiency virus (HIV)-1 and its N-terminal nonapeptide, Tat-(1-9) with amino acid sequence MDPVDPNIE, suggesting that DPPIV, mediates immunosuppressive effects of Tat protein. The 2.0- and 3.15-A, resolution crystal structures of the binary complex between human DPPIV, and nonapeptide Tat-(1-9) and the ternary complex between the variant, MWPVDPNIE, called Trp(2)-Tat-(1-9), and DPPIV bound to adenosine deaminase, show that Tat-(1-9) and Trp(2)-Tat-(1-9) are located in the active site of, DPPIV. The interaction pattern of DPPIV with Trp(2)-Tat-(1-9) is tighter, than that with Tat-(1-9), in agreement with inhibition constants (K(i)) of, 2 x 10(-6) and 250 x 10(-6) m, respectively. Both peptides cannot be, cleaved by DPPIV because the binding pockets of the N-terminal 2 residues, are interchanged compared with natural substrates: the N-terminal, methionine occupies the hydrophobic S1 pocket of DPPIV that normally, accounts for substrate specificity by binding the penultimate residue., Because the N-terminal sequence of the thromboxane A2 receptor resembles, the Trp(2)-Tat-(1-9) peptide, a possible interaction with DPPIV is, postulated. | ||
==About this Structure== | ==About this Structure== | ||
2BGR is a | 2BGR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
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Revision as of 13:39, 5 November 2007
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CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)
OverviewOverview
CD26 or dipeptidyl-peptidase IV (DPPIV) is engaged in immune functions by, co-stimulatory effects on activation and proliferation of T lymphocytes, binding to adenosine deaminase, and regulation of various chemokines and, cytokines. DPPIV peptidase activity is inhibited by both Tat protein from, human immunodeficiency virus (HIV)-1 and its N-terminal nonapeptide, Tat-(1-9) with amino acid sequence MDPVDPNIE, suggesting that DPPIV, mediates immunosuppressive effects of Tat protein. The 2.0- and 3.15-A, resolution crystal structures of the binary complex between human DPPIV, and nonapeptide Tat-(1-9) and the ternary complex between the variant, MWPVDPNIE, called Trp(2)-Tat-(1-9), and DPPIV bound to adenosine deaminase, show that Tat-(1-9) and Trp(2)-Tat-(1-9) are located in the active site of, DPPIV. The interaction pattern of DPPIV with Trp(2)-Tat-(1-9) is tighter, than that with Tat-(1-9), in agreement with inhibition constants (K(i)) of, 2 x 10(-6) and 250 x 10(-6) m, respectively. Both peptides cannot be, cleaved by DPPIV because the binding pockets of the N-terminal 2 residues, are interchanged compared with natural substrates: the N-terminal, methionine occupies the hydrophobic S1 pocket of DPPIV that normally, accounts for substrate specificity by binding the penultimate residue., Because the N-terminal sequence of the thromboxane A2 receptor resembles, the Trp(2)-Tat-(1-9) peptide, a possible interaction with DPPIV is, postulated.
About this StructureAbout this Structure
2BGR is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of HIV-1 Tat-derived nonapeptides Tat-(1-9) and Trp2-Tat-(1-9) bound to the active site of dipeptidyl-peptidase IV (CD26)., Weihofen WA, Liu J, Reutter W, Saenger W, Fan H, J Biol Chem. 2005 Apr 15;280(15):14911-7. Epub 2005 Jan 28. PMID:15695814
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