Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric inhibitor compound 1

Structure

x-ray diffraction · 4 distinct chains · 32% helix, 27% strand (DSSP).

Ligands and binding sites

• SAM · S-adenosylmethionine · ligand · 2 copies · chains A, B, C, D
• 7U2 · (3'R)-N-(cyclopropylmethyl)-1'-[(2-fluorophenyl) methyl]-4-methyl-5H,7H-spiro[pyrano[4,3-d]pyrimidine-8,3'-pyrrolidin]-2-amine · ligand · chains A, B

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

19 pockets found on a 1 Å grid, 8 with a druggability of 0.5 or more.

Interfaces

6 interfaces between chains.

• C–D · 2660 Ų buried · 42 hydrogen bonds · protein-protein
• A–B · 2592 Ų buried · 38 hydrogen bonds · protein-protein
• A–D · 552 Ų buried · 11 hydrogen bonds · protein-protein
• B–C · 537 Ų buried · 11 hydrogen bonds · protein-protein
• A–C · 437 Ų buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 1 covalent (covalent ligand).

Compared structures

• 7RW5 · Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM… · the same entry in another collection · chain A against A, TM-score 1.00
• P31153 · AlphaFold monomer V2.0 prediction for S-adenosylmethionine synthase isoform type-2… · a predicted model of the same protein · chain A against A, TM-score 0.99

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P31153
• Elsewhere: RCSB PDB 7RW5 · PDBe 7RW5 · UniProt P31153