A structural model for chorismate synthase from Mycobacterium tuberculosis in complex with coenzyme and substrate.
The enzymes of the shikimate pathway constitute an excellent target for the design of new antibacterial agents; chorismate synthase (CS) catalyzes the last step of this pathway. The prediction of Mycobacterium tuberculosis (MTB) CS three-dimensional structure and the geometric docking of the coenzyme FMN and the substrate EPSP were performed using the crystal structure of CS from Streptococcus pneumoniae as template. Energy minimization of the whole complex showed, as expected, that most of the template interactions are preserved in the MTB structure, except for HIS11, ARG139 and GLN255. However, novel interactions involving ARG111, GLY113 and SER317 were also observed.
Laboratório de Bioinformática, Modelagem e Simulação de Biossistemas-LABIO, Faculdade de Informática, PUCRS, Brazil.
Cláudia Lemelle
CL
Fernandes
Ardala
A
Breda
Diógenes Santiago
DS
Santos
Luiz Augusto
LA
Basso
Osmar Norberto de
ON
Souza
D000595:Amino Acid Sequence; D003067:Coenzymes / Q000378:metabolism*; D005486:Flavin Mononucleotide / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D003067:Coenzymes; D005486:Flavin Mononucleotide; C019895:chorismate synthase; D019761:Phosphorus-Oxygen Lyases