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| | + | '''Unreleased structure''' |
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| - | ==Crystal structure of the human S-adenosylmethionine synthetase 1 in complex with SAM and PPNP==
| + | The entry 8swa is ON HOLD until Paper Publication |
| - | <StructureSection load='8swa' size='340' side='right'caption='[[8swa]], [[Resolution|resolution]] 2.00Å' scene=''>
| + | |
| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[8swa]] is a 1 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=8SWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SWA 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]] 1.999Å</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPK:(DIPHOSPHONO)AMINOPHOSPHONIC+ACID'>PPK</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=8swa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8swa OCA], [https://pdbe.org/8swa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8swa RCSB], [https://www.ebi.ac.uk/pdbsum/8swa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8swa ProSAT]</span></td></tr>
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| - | </table>
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| - | == Disease ==
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| - | [https://www.uniprot.org/uniprot/METK1_HUMAN METK1_HUMAN] Defects in MAT1A are the cause of methionine adenosyltransferase deficiency (MATD) [MIM:[https://omim.org/entry/250850 250850]; also called MAT I/III deficiency. MATD is an inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic symptoms may be present in rare cases with severe loss of methionine adenosyltransferase activity.<ref>PMID:7560086</ref> <ref>PMID:8770875</ref> <ref>PMID:9042912</ref> <ref>PMID:10677294</ref>
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| - | == Function ==
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| - | [https://www.uniprot.org/uniprot/METK1_HUMAN METK1_HUMAN] Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | One-carbon metabolism is an essential branch of cellular metabolism that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates one-carbon metabolism by inhibiting the biosynthesis of S-adenosylmethionine (SAM), the major methyl donor in cells. FA reacts with privileged, hyperreactive cysteine sites in the proteome, including Cys120 in S-adenosylmethionine synthase isoform type-1 (MAT1A). FA exposure inhibited MAT1A activity and decreased SAM production with MAT-isoform specificity. A genetic mouse model of chronic FA overload showed a decrease n SAM and in methylation on selected histones and genes. Epigenetic and transcriptional regulation of Mat1a and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.
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| - | Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.,Pham VN, Bruemmer KJ, Toh JDW, Ge EJ, Tenney L, Ward CC, Dingler FA, Millington CL, Garcia-Prieto CA, Pulos-Holmes MC, Ingolia NT, Pontel LB, Esteller M, Patel KJ, Nomura DK, Chang CJ Science. 2023 Nov 3;382(6670):eabp9201. doi: 10.1126/science.abp9201. Epub 2023 , Nov 3. PMID:37917677<ref>PMID:37917677</ref>
| + | Authors: Bruemmer, K.J., Pham, V.N., Toh, J.D.W. |
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | Description: Crystal structure of the human S-adenosylmethionine synthetase 1 in complex with SAM and PPNP |
| - | </div>
| + | [[Category: Unreleased Structures]] |
| - | <div class="pdbe-citations 8swa" style="background-color:#fffaf0;"></div>
| + | [[Category: Toh, J.D.W]] |
| - | == References ==
| + | [[Category: Pham, V.N]] |
| - | <references/>
| + | [[Category: Bruemmer, K.J]] |
| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Homo sapiens]]
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| - | [[Category: Large Structures]] | + | |
| - | [[Category: Bruemmer KJ]] | + | |
| - | [[Category: Pham VN]] | + | |
| - | [[Category: Toh JDW]] | + | |
Description: Crystal structure of the human S-adenosylmethionine synthetase 1 in complex with SAM and PPNP
