1J9V

Solution structure of a lactam analogue (DabD) of HIV gp41 600-612 loop.

Summary for 1J9V

• Entry DOI: 10.2210/pdb1j9v/pdb
• Related: 1IM7 1J8N 1J8Z
• NMR Information: BMRB: 5109
• Descriptor: DabD (Ace)IWG(DAB)SGKLIDTTA ANALOGUE OF HIV GP41 (1 entity in total)
• Functional Keywords: lactam peptide, lactam bond, hiv, gp41, cyclic peptide, viral protein
• Cellular location: Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: P12488
• Total number of polymer chains: 1
• Total formula weight: 1388.59

Authors

Phan Chan Du, A.,Limal, D.,Semetey, V.,Dali, H.,Jolivet, M.,Desgranges, C.,Cung, M.T.,Briand, J.P.,Petit, M.C.,Muller, S. (deposition date: 2001-05-29, release date: 2003-07-01, Last modification date: 2024-10-30)

Primary citation

Du, A.P.,Limal, D.,Semetey, V.,Dali, H.,Jolivet, M.,Desgranges, C.,Cung, M.T.,Briand, J.P.,Petit, M.C.,Muller, S.
Structural and immunological characterisation of heteroclitic peptide analogues corresponding to the 600-612 region of the HIV envelope gp41 glycoprotein.
J.Mol.Biol., 323:503-521, 2002

PubMed Abstract: The conformational and immunological properties of different analogues corresponding to the 600-612 disulfide loop of the human immunodeficiency virus (HIV) gp41 glycoprotein envelope were studied. Fourteen analogues were designed and synthesised; namely, a series of seven analogues in which the disulfide bond was replaced by a lactam bridge and a series of seven analogues in which one residue of each analogue at a time, was replaced by its corresponding homologised alpha-amino acid (beta(3)-amino acid). In the case of the lactam analogues, the influence of the two possible CO-NH and NH-CO orientations of the lactam bridge as well as the size of the lactam ring was explored. The analogues were tested in ELISA with monoclonal antibodies raised against the 600-612 cyclic parent peptide as well as with sera from HIV-1 infected patients. A structural analysis of the parent and analogue peptides was carried out in dimethyl sulfoxide (DMSO-d(6)) using two-dimensional NMR techniques and molecular dynamics simulations. Comparison of the own conformation of the cyclic analogues with their either strong or weak reactivity with the antibodies reveals structural features that may be correlated with the antibody reactivity. Thus, a close structural similarity, particularly a characteristic orientation of the side-chains of residues Lys606, Leu607 and Ile608 in the loop, was found in certain beta(3)-analogues that were better recognised than the parent peptide by anti-peptide mouse monoclonal antibodies and patients' antibodies.

PubMed: 12381305
DOI: 10.1016/S0022-2836(02)00701-5

Experimental method

SOLUTION NMR