Interaction of shikimic acid with shikimate kinase.
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.
Pereira
José Henrique
JH
Department of Physics, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
de Oliveira
Jaim Simões
JS
Canduri
Fernanda
F
Dias
Marcio Vinicius Bertacine
MV
Palma
Mário Sérgio
MS
Basso
Luiz Augusto
LA
de Azevedo
Walter Filgueira
WF
Santos
Diógenes Santiago
DS
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
D001426:Bacterial Proteins; D012765:Shikimic Acid; D000244:Adenosine Diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C022642:shikimate kinase