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PDBsum entry 1d6e
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Immune system/peptide inhibitor
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PDB id
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1d6e
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Contents |
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177 a.a.
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179 a.a.
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225 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Peptide and peptide mimetic inhibitors of antigen presentation by hla-Dr class ii mhc molecules. Design, Structure-Activity relationships, And X-Ray crystal structures.
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Authors
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D.R.Bolin,
A.L.Swain,
R.Sarabu,
S.J.Berthel,
P.Gillespie,
N.J.Huby,
R.Makofske,
L.Orzechowski,
A.Perrotta,
K.Toth,
J.P.Cooper,
N.Jiang,
F.Falcioni,
R.Campbell,
D.Cox,
D.Gaizband,
C.J.Belunis,
D.Vidovic,
K.Ito,
R.Crowther,
U.Kammlott,
X.Zhang,
R.Palermo,
D.Weber,
J.Guenot,
Z.Nagy,
G.L.Olson.
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Ref.
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J Med Chem, 2000,
43,
2135-2148.
[DOI no: ]
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PubMed id
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Abstract
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Molecular features of ligand binding to MHC class II HLA-DR molecules have been
elucidated through a combination of peptide structure-activity studies and
structure-based drug design, resulting in analogues with nanomolar affinity in
binding assays. Stabilization of lead compounds against cathepsin B cleavage by
N-methylation of noncritical backbone NH groups or by dipeptide mimetic
substitutions has generated analogues that compete effectively against protein
antigens in cellular assays, resulting in inhibition of T-cell proliferation.
Crystal structures of four ternary complexes of different peptide mimetics with
the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB
have been obtained. Peptide-sugar hybrids have also been identified using a
structure-based design approach in which the sugar residue replaces a dipeptide.
These studies illustrate the complementary roles played by phage display library
methods, peptide analogue SAR, peptide mimetics substitutions, and
structure-based drug design in the discovery of inhibitors of antigen
presentation by MHC class II HLA-DR molecules.
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