Open AccessCrystal structure of the essential biotin‐dependent carboxylase AccA3 from Mycobacterium tuberculosis
Author(s) -
Bennett Matthew,
Högbom Martin
Publication year - 2017
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12212
Subject(s) - pyruvate carboxylase , biotin , mycobacterium tuberculosis , acetyl coa carboxylase , biochemistry , cofactor , bacteria , chemistry , ligand (biochemistry) , biology , enzyme , tuberculosis , receptor , genetics , pathology , medicine
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 Mycobacterium tuberculosis (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. Database Coordinates and structure factors have been deposited in the Protein Data Bank with the accession number 5MLK .