Crystal structure of cyclophilin from Leishmania donovani ligated with cyclosporin A
[Q9U9R3_LEIDO] PPIases accelerate the folding of proteins.[RuleBase:RU000493] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.[RuleBase:RU004223]
Publication Abstract from PubMed
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.