3C5E
Crystal structure of human acyl-CoA synthetase medium-chain family member 2A (L64P mutation) in complex with ATP
Summary for 3C5E
| Entry DOI | 10.2210/pdb3c5e/pdb |
| Related | 3B7W |
| Descriptor | Acyl-coenzyme A synthetase ACSM2A, mitochondrial precursor, MAGNESIUM ION, CHLORIDE ION, ... (8 entities in total) |
| Functional Keywords | middle-chain acyl-coa synthetase, xenobiotic/medium-chain fatty acid-coa ligase, structural genomics consortium, sgc, atp-binding, fatty acid metabolism, lipid metabolism, magnesium, metal-binding, mitochondrion, nucleotide-binding polymorphism, transit peptide, ligase |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion matrix : Q08AH3 |
| Total number of polymer chains | 1 |
| Total formula weight | 64175.50 |
| Authors | Pilka, E.S.,Kochan, G.T.,Bhatia, C.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Oppermann, U.,Structural Genomics Consortium (SGC) (deposition date: 2008-01-31, release date: 2008-02-26, Last modification date: 2023-08-30) |
| Primary citation | Kochan, G.,Pilka, E.S.,von Delft, F.,Oppermann, U.,Yue, W.W. Structural snapshots for the conformation-dependent catalysis by human medium-chain acyl-coenzyme A synthetase ACSM2A. J.Mol.Biol., 388:997-1008, 2009 Cited by PubMed Abstract: Acyl-CoA synthetases belong to the superfamily of adenylate-forming enzymes, and catalyze the two-step activation of fatty acids or carboxylate-containing xenobiotics. The carboxylate substrate first reacts with ATP to form an acyl-adenylate intermediate, which then reacts with CoA to produce an acyl-CoA ester. Here, we report the first crystal structure of a medium-chain acyl-CoA synthetase ACSM2A, in a series of substrate/product/cofactor complexes central to the catalytic mechanism. We observed a substantial rearrangement between the N- and C-terminal domains, driven purely by the identity of the bound ligand in the active site. Our structures allowed us to identify the presence or absence of the ATP pyrophosphates as the conformational switch, and elucidated new mechanistic details, including the role of invariant Lys557 and a divalent magnesium ion in coordinating the ATP pyrophosphates, as well as the involvement of a Gly-rich P-loop and the conserved Arg472-Glu365 salt bridge in the domain rearrangement. PubMed: 19345228DOI: 10.1016/j.jmb.2009.03.064 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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