2BGR

Crystal structure of HIV-1 Tat derived nonapeptides Tat(1-9) bound to the active site of Dipeptidyl peptidase IV (CD26)

Summary for 2BGR

• Entry DOI: 10.2210/pdb2bgr/pdb
• Related: 1J2E 1N1M 1NU6 1NU8 1PFQ 1R9M 1RWQ 1TK3 1TKR 1U8E 1W1I 2BGN
• Descriptor: DIPEPTIDYL PEPTIDASE IV, HIV-1 TAT PROTEIN DERIVED N-TERMINAL NONAPEPTIDE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: hydrolase, hydrolase-complex, dppiv, alpha/beta-hydrolase fold, beta-propeller fold
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 178505.59

Authors

Weihofen, W.A.,Liu, J.,Reutter, W.,Saenger, W.,Fan, H. (deposition date: 2005-01-04, release date: 2005-01-27, Last modification date: 2023-12-13)

Primary citation

Weihofen, W.A.,Liu, J.,Reutter, W.,Saenger, W.,Fan, H.
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)
J.Biol.Chem., 280:14911-, 2005

PubMed Abstract: 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.

PubMed: 15695814
DOI: 10.1074/JBC.M413400200

Experimental method

X-RAY DIFFRACTION (2 Å)