|3eov, resolution 2.60Å ()|
|Non-Standard Residues:||, , , , ,|
|Gene:||CYP (Leishmania donovani)|
|Related:||1bck, 1c5f, 1csa, 1cwa, 1cwb, 1cwc, 1cwf, 1cwh, 1cwi, 1cwj, 1cwk, 1cwl, 1cwm, 1cwo, 1cya, 1cyb, 1cyn, 1ikf, 1m63, 1mf8, 1mik, 1qng, 1qnh, 1xq7, 2esl, 2oju, 2poy, 2rma, 2rmb, 2rmc, 2wfj, 2x2c, 2x7k, 2z6w, 3bo7, 3cys, 2haq|
Crystal structure of cyclophilin from Leishmania donovani ligated with cyclosporin A
Drug development against Leishmania donovani, the pathogen that causes visceral leishmaniasis in humans, is currently an active area of research given the widespread prevalence of the disease and the emergence of resistant strains. The immunosuppressive drug cyclosporin is known to have antiparasitic activity against a variety of pathogens. The receptor for cyclosporin is the protein cyclophilin, which is a ubiquitous peptidylprolyl isomerase. The crystal structure of cyclophilin from L. donovani complexed with cyclosporin has been solved at 2.6 A resolution. The thermodynamic parameters of the interaction have been determined using spectroscopic and calorimetric techniques. A detailed effort has been made to predict the thermodynamic parameters of binding from computations based on the three-dimensional crystal structure. These results were in good agreement with the corresponding experimental values. Furthermore, the structural and biophysical results have been discussed in the context of leishmanial drug resistance and could also set the stage for the design of potent non-immunosuppressive antileishmanials.
Structure of cyclophilin from Leishmania donovani bound to cyclosporin at 2.6 A resolution: correlation between structure and thermodynamic data., Venugopal V, Datta AK, Bhattacharyya D, Dasgupta D, Banerjee R, Acta Crystallogr D Biol Crystallogr. 2009 Nov;65(Pt 11):1187-95. Epub 2009, Oct 22. PMID:19923714
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Venugopal V, Datta AK, Bhattacharyya D, Dasgupta D, Banerjee R. Structure of cyclophilin from Leishmania donovani bound to cyclosporin at 2.6 A resolution: correlation between structure and thermodynamic data. Acta Crystallogr D Biol Crystallogr. 2009 Nov;65(Pt 11):1187-95. Epub 2009, Oct 22. PMID:19923714 doi:10.1107/S0907444909034234
- Venugopal V, Sen B, Datta AK, Banerjee R. Structure of cyclophilin from Leishmania donovani at 1.97 A resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Feb 1;63(Pt, 2):60-4. Epub 2007 Jan 17. PMID:17277440 doi:10.1107/S1744309106056351
- Dutta M, Delhi P, Sinha KM, Banerjee R, Datta AK. Lack of abundance of cytoplasmic cyclosporin A-binding protein renders free-living Leishmania donovani resistant to cyclosporin A. J Biol Chem. 2001 Jun 1;276(22):19294-300. Epub 2001 Feb 21. PMID:11278494 doi:10.1074/jbc.M009379200