Interaction of shikimic acid with shikimate kinase

Autor(es)

Pereira, José Henrique ; Oliveira, Jaim Simões de ; Canduri, Fernanda ; Dias, Marcio Vinicius Bertacine ^[4] ; Palma, Mário Sérgio ; Basso, Luiz Augusto ; Azevedo Júnior, Walter Filgueira de ; Santos, Diógenes Santiago

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 325, n. 1, p. 10-17, Dec. 2004.
• Área do conhecimento: Ciências Biológicas - Biofísica
• Assunto(s): Biofísica Ácido chiquímico Tuberculose Mycobacterium tuberculosis

Resumo

The crystal structure of shikimate kinase from Mycobacterium tuberculosis (MtSK) complexed with MgADP and shikimic acid (shikimate) has been determined at 2.3 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. (AU)

• Processo FAPESP: 01/07532-0 - Structural genomics of cyclin dependent kinases and plant defensive proteinases and their natural inhibitors
• Beneficiário: Walter Filgueira de Azevedo Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/05347-4 - Estudo estrutural das enzimas da via metabólica do ácido chiquímico
• Beneficiário: José Henrique Pereira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto