Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/95151
Title: NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35
Authors: Alag, Reema
Qureshi, Insaf A
Bharatham, Nagakumar
Shin, Joon
Yoon, Ho Sup
Lescar, Julien
Keywords: DRNTU::Science::Chemistry::Analytical chemistry::Proteins
Issue Date: 2010
Source: Alag, R., Qureshi, I. A., Bharatham, N., Shin, J., Lescar, J., & Yoon, H. S. (2010). NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35. Protein Science, 19(8), 1577-1586.
Series/Report no.: Protein science
Abstract: The emergence of drug-resistant malaria parasites is the major threat to effective malaria control, prompting a search for novel compounds with mechanisms of action that are different from the traditionally used drugs. The immunosuppressive drug FK506 shows an antimalarial activity. The mechanism of the drug action involves the molecular interaction with the parasite target proteins PfFKBP35 and PvFKBP35, which are novel FK506 binding protein family (FKBP) members from Plasmodium falciparum and Plasmodium vivax, respectively. Currently, molecular mechanisms of the FKBP family proteins in the parasites still remain elusive. To understand their functions, here we have determined the structures of the FK506 binding domain of Plasmodium vivax (PvFKBD) in unliganded form by NMR spectroscopy and in complex with FK506 by X-ray crystallography. We found out that PvFKBP35 exhibits a canonical FKBD fold and shares kinetic profiles similar to those of PfFKBP35, the homologous protein in P. falciparum, indicating that the parasite FKBP family members play similar biological roles in their life cycles. Despite the similarity, differences were observed in the ligand binding modes between PvFKBD and HsFKBP12, a human FKBP homolog, which could provide insightful information into designing selective antimalarial drug against the parasites.
URI: https://hdl.handle.net/10356/95151
http://hdl.handle.net/10220/8712
DOI: http://dx.doi.org/10.1002/pro.438
Rights: © 2010 The Protein Society
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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