8swa
From Proteopedia
Crystal structure of the human S-adenosylmethionine synthetase 1 in complex with SAM and PPNP
Structural highlights
DiseaseMETK1_HUMAN Defects in MAT1A are the cause of methionine adenosyltransferase deficiency (MATD) [MIM: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.[1] [2] [3] [4] FunctionMETK1_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP. Publication Abstract from PubMedOne-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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
