2BC4

Crystal structure of HLA-DM

Summary for 2BC4

• Entry DOI: 10.2210/pdb2bc4/pdb
• Descriptor: HLA class II histocompatibility antigen, DM alpha chain, HLA class II histocompatibility antigen, DM beta chain, beta-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: mhc class ii, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 96786.24

Authors

Nicholson, M.J.,Moradi, B.,Seth, N.P.,Xing, X.,Cuny, G.D.,Stein, R.L.,Wucherpfennig, K.W. (deposition date: 2005-10-18, release date: 2006-05-23, Last modification date: 2024-10-30)

Primary citation

Nicholson, M.J.,Moradi, B.,Seth, N.P.,Xing, X.,Cuny, G.D.,Stein, R.L.,Wucherpfennig, K.W.
Small molecules that enhance the catalytic efficiency of HLA-DM.
J.Immunol., 176:4208-4220, 2006

PubMed Abstract: 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.

PubMed: 16547258

Experimental method

X-RAY DIFFRACTION (2.27 Å)