5UPT

Acyl-CoA synthetase PtmA2 from Streptomyces platensis in complex with SBNP468 ligand

5UPT の概要

• エントリーDOI: 10.2210/pdb5upt/pdb
• 関連するPDBエントリー: 5E7Q 5UPQ 5UPS
• 分子名称: Acyl-CoA synthetase PtmA2, (7alpha,8alpha,10alpha,13alpha)-7,16-dihydroxykauran-18-oic acid, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: acyl-coa synthetase, ptma2, structural genomics, apc109894, transferase, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro, psi-biology
• 由来する生物種: Streptomyces platensis subsp. rosaceus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 58985.04

構造登録者

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) (登録日: 2017-02-03, 公開日: 2017-02-22, 最終更新日: 2024-11-20)

主引用文献

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

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: 29867143
DOI: 10.1038/s41589-018-0061-0

実験手法

X-RAY DIFFRACTION (1.92 Å)