Structural bioinformatics study of EPSP synthase from Mycobacterium tuberculosis.
The shikimate pathway is an attractive target for herbicides and antimicrobial agent development because it is essential in algae, higher plants, bacteria, and fungi, but absent from mammals. Homologues to enzymes in the shikimate pathway have been identified in the genome sequence of Mycobacterium tuberculosis. Among them, the EPSP synthase was proposed to be present by sequence homology. Accordingly, in order to pave the way for structural and functional efforts towards anti-mycobacterial agent development, here we describe the molecular modeling of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase isolated from M. tuberculosis that should provide a structural framework on which the design of specific inhibitors may be based on. Significant differences in the relative orientation of the domains in the two models result in "open" and "closed" conformations. The possible relevance of this structural transition in the ligand biding is discussed.
Pereira
José Henrique
JH
Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
Canduri
Fernanda
F
de Oliveira
Jaim Simões
JS
da Silveira
Nelson José Freitas
NJ
Basso
Luiz Augusto
LA
Palma
Mário Sérgio
MS
de Azevedo
Walter Filgueira
WF
Santos
Diógenes Santiago
DS
D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D017124:Conserved Sequence; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000201:enzymology* / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D012765:Shikimic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D000097797:Glyphosate
D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D019883:Alkyl and Aryl Transferases; D005998:Glycine; D009097:Multienzyme Complexes; D012765:Shikimic Acid; D000097797:Glyphosate; C042786:shikimic acid-3-phosphate