2bgn: Difference between revisions

Revision as of 20:15, 3 May 2008

HIV-1 TAT PROTEIN DERIVED N-TERMINAL NONAPEPTIDE TRP2-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

2BGN is a Protein complex structure of sequences from Bos taurus and Homo sapiens. 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 Page seeded by OCA on Sat May 3 20:15:40 2008

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OCA

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 '''HIV-1 TAT PROTEIN DERIVED N-TERMINAL NONAPEPTIDE TRP2-TAT (1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)'''
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 [[Category: Saenger, W.]]
 [[Category: Weihofen, W A.]]
-[[Category: ada]]
+[[Category: Ada]]
-[[Category: adenosine deaminase]]
+[[Category: Adenosine deaminase]]
-[[Category: alpha/beta-hydrolase fold]]
+[[Category: Alpha/beta-hydrolase fold]]
-[[Category: aminopeptidase]]
+[[Category: Aminopeptidase]]
-[[Category: beta-propeller fold]]
+[[Category: Beta-propeller fold]]
-[[Category: cd26]]
+[[Category: Cd26]]
-[[Category: dipetidyl peptidase iv]]
+[[Category: Dipetidyl peptidase iv]]
-[[Category: dppiv]]
+[[Category: Dppiv]]
-[[Category: hiv-1 tat protein]]
+[[Category: Hiv-1 tat protein]]
-[[Category: protein-protein complex]]
+[[Category: Protein-protein complex]]
-[[Category: serine protease]]
+[[Category: Serine protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:15:40 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:06:07 2008''