2bgr
From Proteopedia
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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)''' | '''CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)''' | ||
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[[Category: Saenger, W.]] | [[Category: Saenger, W.]] | ||
[[Category: Weihofen, W A.]] | [[Category: Weihofen, W A.]] | ||
| - | [[Category: | + | [[Category: Alpha/beta-hydrolase fold]] |
| - | [[Category: | + | [[Category: Beta-propeller fold]] |
| - | [[Category: | + | [[Category: Cd26]] |
| - | [[Category: | + | [[Category: Dipetidyl peptidase iv]] |
| - | [[Category: | + | [[Category: Dppiv]] |
| - | [[Category: | + | [[Category: Hiv-1 tat protein]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:15:56 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 17:15, 3 May 2008
CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)
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 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
2BGR is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 20:15:56 2008
