1d5m
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X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB
OverviewOverview
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.
About this StructureAbout this Structure
1D5M is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus with NAG and ACE as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures., Bolin DR, Swain AL, Sarabu R, Berthel SJ, Gillespie P, Huby NJ, Makofske R, Orzechowski L, Perrotta A, Toth K, Cooper JP, Jiang N, Falcioni F, Campbell R, Cox D, Gaizband D, Belunis CJ, Vidovic D, Ito K, Crowther R, Kammlott U, Zhang X, Palermo R, Weber D, Guenot J, Nagy Z, Olson GL, J Med Chem. 2000 Jun 1;43(11):2135-48. PMID:10841792
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