1reu: Difference between revisions
New page: left|200px<br /> <applet load="1reu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1reu, resolution 2.65Å" /> '''Structure of the bo... |
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[[Image:1reu. | [[Image:1reu.jpg|left|200px]]<br /><applet load="1reu" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1reu, resolution 2.65Å" /> | caption="1reu, resolution 2.65Å" /> | ||
'''Structure of the bone morphogenetic protein 2 mutant L51P'''<br /> | '''Structure of the bone morphogenetic protein 2 mutant L51P'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known diseases associated with this structure: HFE hemochromatosis, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=112261 112261]] | |||
==About this Structure== | ==About this Structure== | ||
1REU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MPD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1REU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MPD:'>MPD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1REU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: tgf-beta fold]] | [[Category: tgf-beta fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:48:18 2008'' | ||
Revision as of 17:48, 15 February 2008
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Structure of the bone morphogenetic protein 2 mutant L51P
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: HFE hemochromatosis, modifier of OMIM:[112261]
About this StructureAbout this Structure
1REU is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Molecular recognition of BMP-2 and BMP receptor IA., Keller S, Nickel J, Zhang JL, Sebald W, Mueller TD, Nat Struct Mol Biol. 2004 May;11(5):481-8. Epub 2004 Apr 4. PMID:15064755
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