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8gju

From Proteopedia

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Current revision (05:28, 9 August 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8gju is ON HOLD until Paper Publication
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==Crystal structure of human methylmalonyl-CoA mutase (MMUT) in complex with methylmalonic acidemia type A protein (MMAA), coenzyme A, and GDP==
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<StructureSection load='8gju' size='340' side='right'caption='[[8gju]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8gju]] is a 8 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=8GJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GJU FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.79&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gju OCA], [https://pdbe.org/8gju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gju RCSB], [https://www.ebi.ac.uk/pdbsum/8gju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gju ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MMAA_HUMAN MMAA_HUMAN] Vitamin B12-responsive methylmalonic acidemia type cblA. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/MMAA_HUMAN MMAA_HUMAN] GTPase, binds and hydrolyzes GTP (PubMed:28497574, PubMed:20876572, PubMed:21138732, PubMed:28943303). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis (PubMed:28497574, PubMed:20876572). Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MMUT) (PubMed:28497574, PubMed:20876572). Plays a dual role as both a protectase and a reactivase for MMUT (PubMed:21138732, PubMed:28943303). Protects MMUT from progressive inactivation by oxidation by decreasing the rate of the formation of the oxidized inactive cofactor hydroxocobalamin (OH2Cbl) (PubMed:21138732, PubMed:28943303). Additionally acts a reactivase by promoting the replacement of OH2Cbl by the active cofactor AdoCbl, restoring the activity of MMUT in the presence and hydrolysis of GTP (PubMed:21138732, PubMed:28943303).<ref>PMID:20876572</ref> <ref>PMID:21138732</ref> <ref>PMID:28497574</ref> <ref>PMID:28943303</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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G-proteins function as molecular switches to power cofactor translocation and confer fidelity in metal trafficking. The G-protein, MMAA, together with MMAB, an adenosyltransferase, orchestrate cofactor delivery and repair of B(12)-dependent human methylmalonyl-CoA mutase (MMUT). The mechanism by which the complex assembles and moves a &gt;1300 Da cargo, or fails in disease, are poorly understood. Herein, we report the crystal structure of the human MMUT-MMAA nano-assembly, which reveals a dramatic 180 degrees rotation of the B(12) domain, exposing it to solvent. The complex, stabilized by MMAA wedging between two MMUT domains, leads to ordering of the switch I and III loops, revealing the molecular basis of mutase-dependent GTPase activation. The structure explains the biochemical penalties incurred by methylmalonic aciduria-causing mutations that reside at the MMAA-MMUT interfaces we identify here.
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Authors: Mascarenhas, R.M., Ruetz, M., Gouda, H., Yaw, M., Banerjee, R.
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Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B(12) delivery and repair.,Mascarenhas R, Ruetz M, Gouda H, Heitman N, Yaw M, Banerjee R Nat Commun. 2023 Jul 19;14(1):4332. doi: 10.1038/s41467-023-40077-4. PMID:37468522<ref>PMID:37468522</ref>
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Description: Crystal structure of human methylmalonyl-CoA mutase (MMUT) in complex with methylmalonic acidemia type A protein (MMAA), coenzyme A, and GDP
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Gouda, H]]
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<div class="pdbe-citations 8gju" style="background-color:#fffaf0;"></div>
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[[Category: Banerjee, R]]
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== References ==
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[[Category: Yaw, M]]
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<references/>
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[[Category: Ruetz, M]]
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__TOC__
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[[Category: Mascarenhas, R.M]]
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Banerjee R]]
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[[Category: Gouda H]]
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[[Category: Mascarenhas RM]]
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[[Category: Ruetz M]]
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[[Category: Yaw M]]

Current revision

Crystal structure of human methylmalonyl-CoA mutase (MMUT) in complex with methylmalonic acidemia type A protein (MMAA), coenzyme A, and GDP

PDB ID 8gju

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