Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2bgr
From Proteopedia
| Line 29: | Line 29: | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 17:37:49 2007'' |
Revision as of 15:32, 5 November 2007
|
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 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.
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 Mon Nov 5 17:37:49 2007
