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1d5m

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{{STRUCTURE_1d5m| PDB=1d5m | SCENE= }}
{{STRUCTURE_1d5m| PDB=1d5m | SCENE= }}
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'''X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB'''
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===X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB===
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==Overview==
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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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The line below this paragraph, {{ABSTRACT_PUBMED_10841792}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 10841792 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10841792}}
==About this Structure==
==About this Structure==
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[[Category: Swain, A L.]]
[[Category: Swain, A L.]]
[[Category: Immune system]]
[[Category: Immune system]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:28:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 22:28:34 2008''

Revision as of 19:28, 30 June 2008

Image:1d5m.png

Template:STRUCTURE 1d5m

X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB

Template:ABSTRACT PUBMED 10841792

About this Structure

1D5M is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA.

Reference

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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