5UPT
Acyl-CoA synthetase PtmA2 from Streptomyces platensis in complex with SBNP468 ligand
Summary for 5UPT
| Entry DOI | 10.2210/pdb5upt/pdb |
| Related | 5E7Q 5UPQ 5UPS |
| Descriptor | Acyl-CoA synthetase PtmA2, (7alpha,8alpha,10alpha,13alpha)-7,16-dihydroxykauran-18-oic acid, SULFATE ION, ... (6 entities in total) |
| Functional Keywords | acyl-coa synthetase, ptma2, structural genomics, apc109894, transferase, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro, psi-biology |
| Biological source | Streptomyces platensis subsp. rosaceus |
| Total number of polymer chains | 1 |
| Total formula weight | 58985.04 |
| Authors | Osipiuk, J.,Hatzos-Skintges, C.,Endres, M.,Babnigg, G.,Rudolf, J.D.,Chang, C.Y.,Ma, M.,Shen, B.,Phillips Jr., G.N.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Enzyme Discovery for Natural Product Biosynthesis (NatPro) (deposition date: 2017-02-03, release date: 2017-02-22, Last modification date: 2024-11-20) |
| Primary citation | Wang, N.,Rudolf, J.D.,Dong, L.B.,Osipiuk, J.,Hatzos-Skintges, C.,Endres, M.,Chang, C.Y.,Babnigg, G.,Joachimiak, A.,Phillips, G.N.,Shen, B. Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme. Nat. Chem. Biol., 14:730-737, 2018 Cited by PubMed Abstract: Acyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a two-step reaction of adenylation followed by thioesterification. Here, we report the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA ligases from the biosynthetic pathway of platensimycin and platencin, are necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and ptmA2 resulted in the accumulation of free acid and adenylate intermediates, respectively. Enzymatic and structural characterization of PtmA2 confirmed its ability to only catalyze thioesterification. Structural characterization of PtmA2 revealed it binds both free acid and adenylate substrates and undergoes the established mechanism of domain alternation. Finally, site-directed mutagenesis restored both the adenylation and complete CoA activation reactions. This study challenges the currently accepted paradigm of adenylating enzymes and inspires future investigations on functionally separated acyl-CoA ligases and their ramifications in biology. PubMed: 29867143DOI: 10.1038/s41589-018-0061-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
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