1jc8: Difference between revisions

Revision as of 14:21, 21 February 2008

Solution structure of lactam analogue (DDap) of gp41 600-612 loop of HIV

OverviewOverview

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.

About this StructureAbout this Structure

1JC8 is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Structural and immunological characterisation of heteroclitic peptide analogues corresponding to the 600-612 region of the HIV envelope gp41 glycoprotein., Du AP, Limal D, Semetey V, Dali H, Jolivet M, Desgranges C, Cung MT, Briand JP, Petit MC, Muller S, J Mol Biol. 2002 Oct 25;323(3):503-21. PMID:12381305

Page seeded by OCA on Thu Feb 21 13:20:59 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1jc8.gif|left|200px]]<br />
+[[Image:1jc8.gif|left|200px]]<br /><applet load="1jc8" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1jc8" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1jc8" />
 '''Solution structure of lactam analogue (DDap) of gp41 600-612 loop of HIV'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-JC8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ACE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JC8 OCA].
+JC8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JC8 OCA].
 ==Reference==
 Structural and immunological characterisation of heteroclitic peptide analogues corresponding to the 600-612 region of the HIV envelope gp41 glycoprotein., Du AP, Limal D, Semetey V, Dali H, Jolivet M, Desgranges C, Cung MT, Briand JP, Petit MC, Muller S, J Mol Biol. 2002 Oct 25;323(3):503-21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12381305 12381305]
 [[Category: Single protein]]
-[[Category: Briand, J.P.]]
+[[Category: Briand, J P.]]
-[[Category: Cung, M.T.]]
+[[Category: Cung, M T.]]
 [[Category: Dali, H.]]
 [[Category: Desgranges, C.]]
-[[Category: Du, A.Phan.Chan.]]
+[[Category: Du, A Phan Chan.]]
 [[Category: Jolivet, M.]]
 [[Category: Limal, D.]]
 [[Category: Muller, S.]]
-[[Category: Petit, M.C.]]
+[[Category: Petit, M C.]]
 [[Category: Semetey, V.]]
 [[Category: ACE]]
@@ Line 29: / Line 28: @@
 [[Category: peptidomimetics.]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:12:04 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:20:59 2008''