1rew: Difference between revisions

[[Image:1rew.gif|left|200px]]<br /><applet load="1rew" size="350" color="white" frame="true" align="right" spinBox="true"  

Bone morphogenetic protein-2 (BMP-2) and other members of the TGF-beta superfamily regulate the development, maintenance and regeneration of tissues and organs. Binding epitopes for these extracellular signaling proteins have been defined, but hot spots specifying binding affinity and specificity have so far not been identified. In this study, mutational and structural analyses show that epitopes of BMP-2 and the BRIA receptor form a new type of protein-protein interface. The main chain atoms of Leu 51 and Asp53 of BMP-2 represent a hot spot of binding to BRIA. The BMP-2 variant L51P was deficient in type I receptor binding only, whereas its overall structure and its binding to type II receptors and modulator proteins, such as noggin, were unchanged. Thus, the L51P substitution converts BMP-2 into a receptor-inactive inhibitor of noggin. These results are relevant for other proteins of the TGF-beta superfamily and provide useful clues for structure-based drug design.

Known diseases associated with this structure: HFE hemochromatosis, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=112261 112261]], Juvenile polyposis syndrome, infantile form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601299 601299]], Polyposis syndrome, hereditary mixed, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601299 601299]], Polyposis, juvenile intestinal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601299 601299]]

1REW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1REW OCA].  

[[Category: Mueller, T D.]]

[[Category: Zhang, J L.]]

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