Structural view of the regulatory subunit of aspartate kinase from Mycobacterium tuberculosis

Protein Cell. 2011 Sep;2(9):745-54. doi: 10.1007/s13238-011-1094-2. Epub 2011 Oct 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aspartate Kinase / chemistry*
  • Aspartate Kinase / genetics
  • Aspartate Kinase / metabolism
  • Binding Sites
  • Cloning, Molecular
  • Corynebacterium glutamicum / enzymology
  • Crystallization / methods
  • Crystallography, X-Ray
  • Enzyme Activation
  • Enzyme Assays
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Lysine / pharmacology
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology*
  • Plasmids / genetics
  • Plasmids / metabolism
  • Prephenate Dehydrogenase / metabolism
  • Protein Structure, Secondary
  • Threonine / metabolism*
  • Threonine / pharmacology


  • Threonine
  • Prephenate Dehydrogenase
  • Aspartate Kinase
  • Lysine