Bennett Matthew, Högbom Martin
Department of Biochemistry and Biophysics Arrhenius Laboratories for Natural Sciences Stockholm University Sweden.
FEBS Open Bio. 2017 Apr 4;7(5):620-626. doi: 10.1002/2211-5463.12212. eCollection 2017 May.
Biotin-dependent acetyl-CoA carboxylases catalyze the committed step in type II fatty acid biosynthesis, the main route for production of membrane phospholipids in bacteria, and are considered a key target for antibacterial drug discovery. Here we describe the first structure of AccA3, an essential component of the acetyl-CoA carboxylase system in (MTb). The structure, sequence comparisons, and modeling of ligand-bound states reveal that the ATP cosubstrate-binding site shows distinct differences compared to other bacterial and eukaryotic biotin carboxylases, including all human homologs. This suggests the possibility to design MTb AccA3 subtype-specific inhibitors.
Coordinates and structure factors have been deposited in the Protein Data Bank with the accession number 5MLK.
生物素依赖性乙酰辅酶A羧化酶催化II型脂肪酸生物合成中的关键步骤，这是细菌中膜磷脂产生的主要途径，并且被认为是抗菌药物发现的关键靶点。在此，我们描述了结核分枝杆菌（MTb）中乙酰辅酶A羧化酶系统的必需组分AccA3的首个结构。该结构、序列比较以及配体结合状态的建模表明，与其他细菌和真核生物生物素羧化酶（包括所有人类同源物）相比，ATP共底物结合位点存在明显差异。这表明有可能设计出结核分枝杆菌AccA3亚型特异性抑制剂。
坐标和结构因子已存入蛋白质数据库，登录号为5MLK。
