Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

8OOG

Crystal structure of human MAT2a with S-Adenosylmethionine and a fragment bound in a novel pocket

Summary for 8OOG
Entry DOI10.2210/pdb8oog/pdb
DescriptorS-adenosylmethionine synthase isoform type-2, S-ADENOSYLMETHIONINE, 6-oxidanyl-1,3-benzoxathiol-2-one, ... (5 entities in total)
Functional Keywordsmethionine adenosyltransferase, s-adenosylmethionine synthetase, fragment screen, allosteric binder, transferase
Biological sourceHomo sapiens (human)
Total number of polymer chains1
Total formula weight44658.70
Authors
Schimpl, M. (deposition date: 2023-04-05, release date: 2023-07-12, Last modification date: 2024-06-19)
Primary citationLa Sala, G.,Pfleger, C.,Kack, H.,Wissler, L.,Nevin, P.,Bohm, K.,Janet, J.P.,Schimpl, M.,Stubbs, C.J.,De Vivo, M.,Tyrchan, C.,Hogner, A.,Gohlke, H.,Frolov, A.I.
Combining structural and coevolution information to unveil allosteric sites.
Chem Sci, 14:7057-7067, 2023
Cited by
PubMed Abstract: Understanding allosteric regulation in biomolecules is of great interest to pharmaceutical research and computational methods emerged during the last decades to characterize allosteric coupling. However, the prediction of allosteric sites in a protein structure remains a challenging task. Here, we integrate local binding site information, coevolutionary information, and information on dynamic allostery into a structure-based three-parameter model to identify potentially hidden allosteric sites in ensembles of protein structures with orthosteric ligands. When tested on five allosteric proteins (LFA-1, p38-α, GR, MAT2A, and BCKDK), the model successfully ranked all known allosteric pockets in the top three positions. Finally, we identified a novel druggable site in MAT2A confirmed by X-ray crystallography and SPR and a hitherto unknown druggable allosteric site in BCKDK validated by biochemical and X-ray crystallography analyses. Our model can be applied in drug discovery to identify allosteric pockets.
PubMed: 37389247
DOI: 10.1039/d2sc06272k
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.384 Å)
Structure validation

239492

数据于2025-07-30公开中

PDB statisticsPDBj update infoContact PDBjnumon