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| | ==Structure of the S283Y mutant of MRDI== | | ==Structure of the S283Y mutant of MRDI== |
| - | <StructureSection load='4ldr' size='340' side='right' caption='[[4ldr]], [[Resolution|resolution]] 2.29Å' scene=''> | + | <StructureSection load='4ldr' size='340' side='right'caption='[[4ldr]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ldr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LDR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LDR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ldr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LDR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LDR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ldq|4ldq]]</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]] 2.292Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MRI1, MRDI, UNQ6390/PRO21135 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ldr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ldr OCA], [https://pdbe.org/4ldr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ldr RCSB], [https://www.ebi.ac.uk/pdbsum/4ldr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ldr ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-methyl-5-thioribose-1-phosphate_isomerase S-methyl-5-thioribose-1-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.23 5.3.1.23] </span></td></tr>
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| - | <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=4ldr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ldr OCA], [http://pdbe.org/4ldr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ldr RCSB], [http://www.ebi.ac.uk/pdbsum/4ldr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ldr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MTNA_HUMAN MTNA_HUMAN]] Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P). Independently from catalytic activity, promotes cell invasion in response to constitutive RhoA activation by promoting FAK tyrosine phosphorylation and stress fiber turnover.<ref>PMID:19620624</ref> | + | [https://www.uniprot.org/uniprot/MTNA_HUMAN MTNA_HUMAN] Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P). Independently from catalytic activity, promotes cell invasion in response to constitutive RhoA activation by promoting FAK tyrosine phosphorylation and stress fiber turnover.<ref>PMID:19620624</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Metastatic melanoma is among the most intractable cancers to treat, where patients show resistance to therapy and limited survival time. A critical step in the development of metastatic melanoma is the acquisition of invasion and transition from thin to thick tumors on the skin, followed by invasion to lymph nodes. Prior studies have shown that metastatic melanoma is associated with dysregulation of RhoA and enhanced expression of a protein named "mediator of RhoA-dependent invasion (MRDI)". Importantly, MRDI is a "moonlighting" enzyme, with two distinct functions in melanoma cells. First, MRDI acts as a methylthioribose-1-phosphate (MTR-1-P) isomerase, catalyzing a critical step in methionine salvage. Second, MRDI promotes and is necessary for melanoma cell invasion, independent of its catalytic activity. Here, we demonstrate that MtnA, a bacterial MTR-1-P isomerase, rescues the methionine salvage function of MRDI, but is unable to rescue its role in invasion. We then solve the crystal structure of MRDI to a resolution of 2.5 A, in order to identify structural elements important for its invasion activity. We present this structure and its comparison with other MTR-1-P isomerases, and identify mutations within a region separate from the MTR-1-P binding site which interfere with invasion. Thus, structural elements in MRDI distal from the MTR-1-P catalytic site are responsible for the invasion phenotype.
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| - | Structure of MRDI Explains its Dual Function as a Metabolic Enzyme and a Mediator of Cell Invasion.,Templeton PD, Litman ES, Metzner SI, Ahn NG, Sousa MC Biochemistry. 2013 Jul 16. PMID:23859498<ref>PMID:23859498</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 4ldr" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: S-methyl-5-thioribose-1-phosphate isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Metzner, S I]] | + | [[Category: Metzner SI]] |
| - | [[Category: Sousa, M C]] | + | [[Category: Sousa MC]] |
| - | [[Category: Templeton, P D]] | + | [[Category: Templeton PD]] |
| - | [[Category: Cell invasion]]
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| - | [[Category: Helix bundle]]
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| - | [[Category: Isomerase]]
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| - | [[Category: Rossmann-like fold]]
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