title: Interaction of shikimic acid with shikimate kinase.
abstract: The crystal structure of shikimate kinase from Mycobacterium tuberculosis (MtSK) complexed with MgADP and shikimic acid (shikimate) has been determined at 2.3A resolution, clearly revealing the amino acid residues involved in shikimate binding. In MtSK, the Glu61 strictly conserved in SK forms a hydrogen bond and salt-bridge with Arg58 and assists in positioning the guanidinium group of Arg58 for shikimate binding. The carboxyl group of shikimate interacts with Arg58, Gly81, and Arg136, and hydroxyl groups with Asp34 and Gly80. The crystal structure of MtSK-MgADP-shikimate will provide crucial information for elucidation of the mechanism of SK-catalyzed reaction and for the development of a new generation of drugs against tuberculosis.
authors.affiliation: Department of Physics, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Pereira
authors.forename: Jaim Simões
authors.initials: JS
authors.lastname: de Oliveira
authors.forename: Fernanda
authors.initials: F
authors.lastname: Canduri
authors.forename: Marcio Vinicius Bertacine
authors.initials: MV
authors.lastname: Dias
authors.forename: Mário Sérgio
authors.initials: MS
authors.lastname: Palma
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Basso
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: de Azevedo
authors.forename: Diógenes Santiago
authors.initials: DS
authors.lastname: Santos
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012765:Shikimic Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012765:Shikimic Acid; D000244:Adenosine Diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C022642:shikimate kinase