Structural Analysis of Cyclophilin from Moniliophthora Perniciosa and Inhibitory Activity of Cyclosporin an on Germination and Growth of Fungi
- *Corresponding Author:
- Paulo S Monzani
Central Avançada em Biotecnologia da Reprodução Animal
Universidade Norte do Paraná, Londrina – PR, Brazil
Tel: 55 43 3399 4700
Fax: 55 43 4043 0888
E-mail: [email protected]
Received date: November 01, 2011; Accepted date: December 03, 2011; Published date: December 05, 2011
Citation: Monzani PS, Pereira HM, Gramacho KP, Alvim FC, Meirelles FV, et al. (2011) Structural Analysis of Cyclophilin from Moniliophthora Perniciosa and Inhibitory Activity of Cyclosporin an on Germination and Growth of Fungi. Pharm Anal Acta S7:001. doi: 10.4172/2153-2435.S7-001
Copyright: © 2011 Monzani PS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Moniliophthora perniciosa is the causal agent of witches’ broom disease of cacao. Cyclophilins have been implicated in a wide variety of cellular processes, including the response to environmental stresses, cell cycle control, regulation of calcium signaling and transcriptional control. The involvement of cyclophilins in pathogenicity was described both in pathogenic fungi toward animals and plants. In Yeast, calcineurin and cyclophilin are involved in fungal morphogenesis and virulence. There is evidence that cyclophilin interacts with calcineurin in the absence of cyclosporin A (CsA), and it has been proposed that the activity of CsA acts in the regulatory interaction between cyclophilin and calcineurin; also, fungistatic or fungicide actions have been observed in this activity. The M. perniciosa cyclophilin gene from cDNA of the fruiting body in the vector pET28a has been cloned and the protein was expressed, purified and crystallized. The cyclophilin structures in the apo and bound with CsA forms were solved at 1.85 and 1.47 ÃÂº, respectively. Comparison of structures from different organisms indicates conserved structures of cyclophilins. Small differences were found in apo and bound forms; hence, it follows that cyclophilin structures do not have accentuated modifications in the presence of the ligand. However, various hydrogen bonds between side chains of amino acids and water molecules are broken in the ligand site when CsA is bound. The germination spore assays using CsA showed a low inhibitory activity in germination, but high inhibition of the germ tube growth. These results show that cyclophilin plays an important role in the growth process, but not in the germination, hence suggesting that cyclophilin is as potential target for the fungistatic action against M. perniciosa.