title: Structural view of the regulatory subunit of aspartate kinase from Mycobacterium tuberculosis.
abstract: The aspartate kinase (AK) from Mycobacterium tuberculosis (Mtb) catalyzes the biosynthesis of aspartate family amino acids, including lysine, threonine, isoleucine and methionine. We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone (referred to as MtbAKβ) and in complex with threonine (referred to as MtbAKβ-Thr) at resolutions of 2.6 Å and 2.0 Å, respectively. MtbAKβ is composed of two perpendicular non-equivalent ACT domains [aspartate kinase, chorismate mutase, and TyrA (prephenate dehydrogenase)] per monomer. Each ACT domain contains two α helices and four antiparallel β strands. The structure of MtbAKβ shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum (referred to as CgAKβ), suggesting similar regulatory mechanisms. Biochemical assays in our study showed that MtbAK is inhibited by threonine. Based on crystal structure analysis, we discuss the regulatory mechanism of MtbAK.
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Qingzhu
authors: Q
authors: Yang
authors: Kun
authors: K
authors: Yu
authors: Liming
authors: L
authors: Yan
authors: Yuanyuan
authors: Y
authors: Li
authors: Cheng
authors: C
authors: Chen
authors: Xuemei
authors: X
authors: Li
mesh_terms: D000595:Amino Acid Sequence; D001222:Aspartate Kinase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D048230:Corynebacterium glutamicum / Q000201:enzymology; D003460:Crystallization / Q000379:methods; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D057075:Enzyme Assays; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011303:Prephenate Dehydrogenase / Q000378:metabolism; D017433:Protein Structure, Secondary; D013912:Threonine / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D013912:Threonine; D011303:Prephenate Dehydrogenase; D001222:Aspartate Kinase; D008239:Lysine