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| | ==Crystal structure of menin reveals the binding site for Mixed Lineage Leukemia (MLL) protein== | | ==Crystal structure of menin reveals the binding site for Mixed Lineage Leukemia (MLL) protein== |
| - | <StructureSection load='3re2' size='340' side='right' caption='[[3re2]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='3re2' size='340' side='right'caption='[[3re2]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3re2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Nemve Nemve]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RE2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RE2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3re2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Nematostella_vectensis Nematostella vectensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RE2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">v1g241841 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=45351 NEMVE])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3re2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3re2 OCA], [http://pdbe.org/3re2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3re2 RCSB], [http://www.ebi.ac.uk/pdbsum/3re2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3re2 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3re2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3re2 OCA], [https://pdbe.org/3re2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3re2 RCSB], [https://www.ebi.ac.uk/pdbsum/3re2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3re2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A7RZU9_NEMVE A7RZU9_NEMVE] |
| - | Menin is a tumor suppressor protein that is encoded by the MEN1 (multiple endocrine neoplasia 1) gene and controls cell growth in endocrine tissues. Importantly, menin also serves as a critical oncogenic cofactor of MLL (mixed lineage leukemia) fusion proteins in acute leukemias. Direct association of menin with MLL fusion proteins is required for MLL fusion protein-mediated leukemogenesis in vivo, and this interaction has been validated as a new potential therapeutic target for development of novel anti-leukemia agents. Here, we report the first crystal structure of menin homolog from Nematostella vectensis. Due to a very high sequence similarity, the Nematostella menin is a close homolog of human menin, and these two proteins likely have very similar structures. Menin is predominantly an alpha-helical protein with the protein core comprising three tetratricopeptide motifs that are flanked by two alpha-helical bundles and covered by a beta-sheet motif. A very interesting feature of menin structure is the presence of a large central cavity that is highly conserved between Nematostella and human menin. By employing site-directed mutagenesis, we have demonstrated that this cavity constitutes the binding site for MLL. Our data provide a structural basis for understanding the role of menin as a tumor suppressor protein and as an oncogenic co-factor of MLL fusion proteins. It also provides essential structural information for development of inhibitors targeting the menin-MLL interaction as a novel therapeutic strategy in MLL-related leukemias.
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| - | Crystal Structure of Menin Reveals Binding Site for Mixed Lineage Leukemia (MLL) Protein.,Murai MJ, Chruszcz M, Reddy G, Grembecka J, Cierpicki T J Biol Chem. 2011 Sep 9;286(36):31742-8. Epub 2011 Jul 13. PMID:21757704<ref>PMID:21757704</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3re2" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Nemve]] | + | [[Category: Large Structures]] |
| - | [[Category: Chruszcz, M]] | + | [[Category: Nematostella vectensis]] |
| - | [[Category: Cierpicki, T]] | + | [[Category: Chruszcz M]] |
| - | [[Category: Grembecka, J]] | + | [[Category: Cierpicki T]] |
| - | [[Category: Murai, M J]] | + | [[Category: Grembecka J]] |
| - | [[Category: Reddy, G]] | + | [[Category: Murai MJ]] |
| - | [[Category: Menin]]
| + | [[Category: Reddy G]] |
| - | [[Category: Mixed lineage leukemia]]
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| - | [[Category: Multiple endocrine neoplasia 1]]
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| - | [[Category: Tumor suppressor]]
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| - | [[Category: Unknown function]]
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