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.
Current Medicinal Chemistry
Title:Shikimate Kinase, a Protein Target for Drug Design
Volume: 21 Issue: 5
Author(s): J.D. Coracini and W.F. de Azevedo
Affiliation:
Keywords: Shikimate kinase, Mycobacterium tuberculosis, drug-design, bioinformatics, molecular docking.
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.
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Cite this article as:
Coracini J.D. and Azevedo de W.F., Shikimate Kinase, a Protein Target for Drug Design, Current Medicinal Chemistry 2014; 21 (5) . https://dx.doi.org/10.2174/09298673113206660299
DOI https://dx.doi.org/10.2174/09298673113206660299 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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