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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 21
ISSUE: 5
DOI: 10.2174/09298673113206660299      Price:  $58









Shikimate Kinase, a Protein Target for Drug Design

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Author(s): J.D. Coracini and W.F. de Azevedo
Pages 592-604 (13)
Abstract:
ATP: shikimate 3-phosphotransferase catalyzes the fifth chemical reaction of shikimate pathway. This metabolic route is responsible for the production of chorismate, a precursor of aromatic amino acids. This especially interesting enzymatic step is indispensable for the survival of the etiological agent of tuberculosis and not found in animals. Therefore the enzyme ATP: shikimate 3-phosphotransferase has been classified as a target for chemotherapeutic development of antitubercular drugs. The ATP:shikimate 3-phosphotransferase has also the denomination of shikimate kinase. This review highlights the available crystallographic studies of shikimate kinases that have been used to identify structural features for ligand-biding affinity. We also describe molecular docking studies focused on shikimate kinase. These computational studies were performed in order to identify the new generation of antitubercular drugs and several potential inhibitors have been described. In addition, a structural comparison of shikimate kinase ATP-binding pocket with human cyclin-dependent kinase 2 (CDK2) is described. This analysis shows the structural similarities between both enzymes, and the potential beneficial aspects of abundant structural studies of CDK2 and their inhibitors to bring further understanding of the ligand-binding specificity for shikimate kinase.
Keywords:
Shikimate kinase, Mycobacterium tuberculosis, drug-design, bioinformatics, molecular docking.
Affiliation:
Faculty of Biosciences. Pontifical Catholic University of Rio Grande do Sul. Av. Ipiranga, 6681. Porto Alegre-RS. Brazil. 90690-900.