1D6E

CRYSTAL STRUCTURE OF HLA-DR4 COMPLEX WITH PEPTIDOMIMETIC AND SEB

Summary for 1D6E

• Entry DOI: 10.2210/pdb1d6e/pdb
• Related: 1D5M 1D5X 1D5Z
• Related PRD ID: PRD_000396
• Descriptor: HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, ENTEROTOXIN TYPE B, PEPTIDOMIMETIC INHIBITOR, ... (5 entities in total)
• Functional Keywords: mhc class ii-superantigen complex, immune system-peptide inhibitor complex, peptidomimetic inhibitor, immune system/peptide inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903 P13760; Secreted: P01552
• Total number of polymer chains: 4
• Total formula weight: 72918.07

Authors

Swain, A.,Crowther, R.,Kammlott, U. (deposition date: 1999-10-13, release date: 2000-06-28, Last modification date: 2023-11-15)

Primary citation

Bolin, D.R.,Swain, A.L.,Sarabu, R.,Berthel, S.J.,Gillespie, P.,Huby, N.J.,Makofske, R.,Orzechowski, L.,Perrotta, A.,Toth, K.,Cooper, J.P.,Jiang, N.,Falcioni, F.,Campbell, R.,Cox, D.,Gaizband, D.,Belunis, C.J.,Vidovic, D.,Ito, K.,Crowther, R.,Kammlott, U.,Zhang, X.,Palermo, R.,Weber, D.,Guenot, J.,Nagy, Z.,Olson, G.L.
Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.
J.Med.Chem., 43:2135-2148, 2000

PubMed Abstract: 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.

PubMed: 10841792
DOI: 10.1021/jm000034h

Experimental method

X-RAY DIFFRACTION (2.45 Å)