Structure of chorismate synthase from Mycobacterium tuberculosis.
In bacteria, fungi, plants, and apicomplexan parasites, the aromatics compounds, such as aromatics amino acids, are synthesized through seven enzymes from the shikimate pathway, which are absent in mammals. The absence of this pathway in mammals make them potential targets for development of new therapy against infectious diseases, such as tuberculosis, which is the world's second commonest cause of death from infectious disease. The last enzyme of shikimate pathway is the chorismate synthase (CS), which is responsible for conversion of the 5-enolpyruvylshikimate-3-phosphate to chorismate. Here, we report the crystallographic structure of CS from Mycobacterium tuberculosis (MtCS) at 2.65 A resolution. The MtCS structure is similar to other CS structures, presenting beta-alpha-beta sandwich structural topology, in which each monomer of MtCS consists of a central helical core. The MtCS can be described as a tetramer formed by a dimer of dimers. However, analytical ultracentrifugation studies suggest the MtCS is a dimer with a more asymmetric shape than observed on the crystallographic dimer and the existence of a low equilibrium between dimer and tetramer. Our results suggest that the MtCS oligomerization is concentration dependent and some conformational changes must be involved on that event.
Dias
Marcio V B
MV
Programa de Pós-Graduação em Biofísica Molecular, Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
Borges
Júlio C
JC
Ely
Fernanda
F
Pereira
José H
JH
Canduri
Fernanda
F
Ramos
Carlos H I
CH
Frazzon
Jeverson
J
Palma
Mário S
MS
Basso
Luis A
LA
Santos
Diógenes S
DS
de Azevedo
Walter F
WF
D000595:Amino Acid Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry
D011994:Recombinant Proteins; D014867:Water; C019895:chorismate synthase; D019761:Phosphorus-Oxygen Lyases