4ktt | pdb_00004ktt

Structural insights of MAT enzymes: MATa2b complexed with SAM

spinqualitylabelsall models 4ktt, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ktt is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: EDO, MG, PO4, SAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function METK2_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP. Publication Abstract from PubMed S-Adenosylmethionine (SAMe) is the principal methyl donor of the cell and is synthesized via an ATP-driven process by methionine adenosyltransferase (MAT) enzymes. It is tightly linked with cell proliferation in liver and colon cancer. In humans, there are three genes, mat1A, mat2A and mat2B, which encode MAT enzymes. mat2A and mat2B transcribe MATalpha2 and MATbeta enzyme subunits, respectively, with catalytic and regulatory roles. The MATalpha2beta complex is expressed in nearly all tissues and is thought to be essential in providing the necessary SAMe flux for methylation of DNA and various proteins including histones. In human hepatocellular carcinoma mat2A and mat2B genes are upregulated, highlighting the importance of the MATalpha2beta complex in liver disease. The individual subunits have been structurally characterized but the nature of the complex has remained elusive despite its existence having been postulated for more than 20 years and the observation that MATbeta is often co-localized with MATalpha2. Though SAMe can be produced by MAT(alpha2)4 alone, this paper shows that the V max of the MATalpha2beta complex is three- to fourfold higher depending on the variants of MATbeta that participate in complex formation. Using X-ray crystallography and solution X-ray scattering, the first structures are provided of this 258 kDa functional complex both in crystals and solution with an unexpected stoichiometry of 4alpha2 and 2betaV2 subunits. It is demonstrated that the N-terminal regulates the activity of the complex and it is shown that complex formation takes place surprisingly via the C-terminal of MATbetaV2 that buries itself in a tunnel created at the interface of the MAT(alpha2)2. The structural data suggest a unique mechanism of regulation and provide a gateway for structure-based drug design in anticancer therapies. Structure and function study of the complex that synthesizes S-adenosylmethionine.,Murray B, Antonyuk SV, Marina A, Van Liempd SM, Lu SC, Mato JM, Hasnain SS, Rojas AL IUCrJ. 2014 Jun 12;1(Pt 4):240-9. doi: 10.1107/S2052252514012585. eCollection, 2014 Jul 1. PMID:25075345 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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