title: Structural bioinformatics study of EPSP synthase from Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Pereira
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: Jaim Simões
authors.initials: JS
authors.lastname: de Oliveira
authors.forename: Nelson José Freitas
authors.initials: NJ
authors.lastname: da Silveira
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Basso
authors.forename: Mário Sérgio
authors.initials: MS
authors.lastname: Palma
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
authors.forename: Diógenes Santiago
authors.initials: DS
authors.lastname: Santos
mesh_terms: 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
chemical_list: 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