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Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/26953
Title: Structural analysis of chorismate synthase from Plasmodium falciparum: A novel target for antimalaria drug discovery
Authors: Tapas S.
Kumar A.
Dhindwal S.
Preeti
Kumar, Pravindra R.Manish
Published in: International Journal of Biological Macromolecules
Abstract: The shikimate pathway in Plasmodium falciparum provides several targets for designing novel antiparasitic agents for the treatment of malaria. Chorismate synthase (CS) is a key enzyme in the shikimate pathway which catalyzes the seventh and final step of the pathway. P. falciparum chorismate synthase (PfCS) is unique in terms of enzymatic behavior, cellular localization and in having two additional amino acid inserts compared to any other CS. The structure of PfCS along with cofactor FMN was predicted by homology modeling using crystal structure of Helicobacter pylori chorismate synthase (HpCS). The quality of the model was validated using structure analysis servers and molecular dynamics. Dimeric form of PfCS was generated and the FMN binding mechanism involving movement of loop near active site has been proposed. Active site pocket has been identified and substrate 5-enolpyruvylshikimate 3-phosphate (EPSP) along with screened potent inhibitors has been docked. The study resulted in identification of putative inhibitors of PfCS with binding efficiency in nanomolar range. The selected putative inhibitors could lead to the development of anti-malarial drugs. © 2011 Elsevier B.V.
Citation: International Journal of Biological Macromolecules, 49(4): 767-777
URI: https://doi.org/10.1016/j.ijbiomac.2011.07.011
http://repository.iitr.ac.in/handle/123456789/26953
Issue Date: 2011
Keywords: Chorismate synthase
Homology modeling
Plasmodium falciparum
Shikimate pathway
ISSN: 1418130
Author Scopus IDs: 35491918300
57215268661
36082537700
35103173800
55064809000
Author Affiliations: Tapas, S., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
Kumar, A., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
Dhindwal, S., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
Preeti, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
Kumar, P., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India
Funding Details: This work was supported by financial aid from the Department of Science and Technology , New Delhi, India. We thank Dr. Shailly Tomar for helpful discussions. We also acknowledge Macromolecular Crystallographic Unit (MCU) for providing computational facilities. Satya thanks AICTE, Abhinav thanks DBT, Sonali thanks MHRD and Preeti thanks CSIR for financial support. Council for Scientific and Industrial Research, South Africa, CSIR; Department of Biotechnology, Ministry of Science and Technology, India, DBT; All India Council for Technical Education, अभातशिप; Ministry of Human Resource Development, MHRD
Corresponding Author: Tapas, S.; Department of Biotechnology, , Roorkee 247667, Uttarakhand, India; email: satyadbt@iitr.ernet.in
Appears in Collections:Journal Publications [BT]

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