2bc4: Difference between revisions

Revision as of 20:05, 3 May 2008

Crystal structure of HLA-DM

OverviewOverview

HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Large lateral surfaces involved in the DM:HLA-DR (DR) interaction have been defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide exchange. Mechanistic studies demonstrate that these small molecules substantially enhance the catalytic efficiency of DM, indicating that they make the transition state of the DM:DR/peptide complex energetically more favorable. These compounds fall into two functional classes: two compounds are active only in the presence of DM, and binding data for one show a direct interaction with DM. The remaining two compounds have partial activity in the absence of DM, suggesting that they may act at the interface between DM and DR/peptide. A hydrophobic ridge in the DMbeta1 domain was implicated in the catalysis of peptide exchange because the activity of three of these enhancers was substantially reduced by point mutations in this area.

About this StructureAbout this Structure

2BC4 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Small molecules that enhance the catalytic efficiency of HLA-DM., Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW, J Immunol. 2006 Apr 1;176(7):4208-20. PMID:16547258 Page seeded by OCA on Sat May 3 20:05:46 2008

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OCA

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 [[Image:2bc4.gif|left|200px]]
- {{Structure
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-|GENE= HLA-DMA, DMA, RING6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HLA-DMB, DMB, RING7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc4 OCA], [http://www.ebi.ac.uk/pdbsum/2bc4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bc4 RCSB]</span>
-}}
 '''Crystal structure of HLA-DM'''
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 [[Category: Wucherpfennig, K W.]]
 [[Category: Xing, X.]]
-[[Category: mhc class ii]]
+[[Category: Mhc class ii]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:05:46 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:04:10 2008''