8SWA
Crystal structure of the human S-adenosylmethionine synthetase 1 in complex with SAM and PPNP
Summary for 8SWA
| Entry DOI | 10.2210/pdb8swa/pdb |
| Descriptor | S-adenosylmethionine synthase isoform type-1, (DIPHOSPHONO)AMINOPHOSPHONIC ACID, MAGNESIUM ION, ... (6 entities in total) |
| Functional Keywords | complex, 1-carbon, sam, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 45580.20 |
| Authors | |
| Primary citation | Pham, V.N.,Bruemmer, K.J.,Toh, J.D.W.,Ge, E.J.,Tenney, L.,Ward, C.C.,Dingler, F.A.,Millington, C.L.,Garcia-Prieto, C.A.,Pulos-Holmes, M.C.,Ingolia, N.T.,Pontel, L.B.,Esteller, M.,Patel, K.J.,Nomura, D.K.,Chang, C.J. Formaldehyde regulates S -adenosylmethionine biosynthesis and one-carbon metabolism. Science, 382:eabp9201-eabp9201, 2023 Cited by PubMed Abstract: 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 -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 and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units. PubMed: 37917677DOI: 10.1126/science.abp9201 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.999 Å) |
Structure validation
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