Homology Modeling Studies of Beta(1,3)-D-Glucan Synthase of Moniliophthora perniciosa Antonio Anderson Freitas Pinheiro,* [a] Alex Gutterres Taranto, [b] Angelo Ama ˆncio Duarte, [c] Arist oteles G oes Neto, [a] Braz Tavares da Hora J unior, [a] Gonc ¸alo Amarante Guimara ˜es Pereira, [d] Manoelito Coelho dos Santos J unior, [a] and Sandra Aparecida de Assis [a] The Witches’ Broom Disease, caused by the hemibiotrophic basidiomycete fungus Moniliophthora perniciosa, drastically reduced the production of cocoa in Brazil. Phytosanitation, chemical control, genetically resistant strains, and biological control still leave flaws in the disease eradication process. Effort has been expended in the elucidation of molecular targets, in particular, the structural components of the fungal cell wall, such as the beta(1,3)-D-glucan synthase. This enzyme is essential for the cellular construction of the wall, as it catalyses the formation of beta(1,3)-D-glucans. Protein structure homology modeling approaches are able to determine the structure of proteins without performing experimental steps, considering the barriers related to experimental methods for the structural determination of molecular targets. The presence of the conserved catalytic residues in members of the same glycosyltransferase family and overall structural analysis suggests that they catalyze glycosyl transfer reactions by similar mechanisms. Therefore, the objective of this study was to determine the three-dimensional model of the enzyme beta(1,3)-D-glucan synthase of M. perniciosa by homology modeling. Both procedures were performed to build the models: a comparative modeling by satisfaction of spatial restraints in MODELLER and a modeling by assembly of rigid bodies in the SWISS-MODEL software. The models were elected based on analysis of the stereochemistry quality and a quantitative assessment of similarity from the obtained models and to templates. A reasonable structural model was obtained of the beta(1,3)-D-glucan synthase enzyme (BegS1). The BegS1 model showed two distinct a/b domains, features of the inverting glycosyltransferase family, and the topology of the folded structure showed 7 beta-strands and 13 alpha-helices. The BegS1 model showed the presence of a catalytic cavity formed by the conserved aspartic acid residues (Asp326, 345, 353, and 354 DDxD motif ) implicated in substrate binding and/ or catalysis. In the BegS1 model, this cavity is near a loop region, as was observed in the GT-2 family structure. It is encouraging to find that the model for BegS1 agrees well with structures from the GT-2 enzyme family. V C 2012 Wiley Periodicals, Inc. DOI: 10.1002/qua.24212 Introduction The culture of Theobroma cacao L. (Cocoa) has great economic importance. This plant is cultivated by more than two million farmers in over 50 countries. [1] Moniliophthora perniciosa, the causal agent of Witches’ Broom Disease (WBD) in cacao, is a hemibiotrophic basidiomycete fungus. [2] This plant pathogen represents one of the most devastating diseases of cacao in America. [3] Several crops have been abandoned because of the disease; traditional farmers remain in other areas but with low incom- e. [4] The WBD shows distinct stages, a biotrophic and a sapro- trophic phase. In the biotrophic phase, wider convoluted inter- cellular hyphae are produced that lack clamp connections, along with hypertrophy and hyperplasia of the tissues (green broom). In the saprotrophic phase, necrosis and death occur in infected tissues distal from the original infection site (dry broom). [5,6] There are four major strategies in the treatment of cacao disease: phytosanitation, chemical control, genetic resistance, and biological control. These four methodologies still have flaws. [7] Currently, effort has been expended in the elucidation of molecular targets, in particular the structural components of the fungal cell wall. [8–10] The fungal cell wall, which func- tions in a number of important processes, is a crucial compo- nent for the life of the pathogen because it promotes suffi- cient mechanical strength to withstand changes in osmotic pressure imposed by the environment. [11] The beta(1,3)-D-glucan is a major and most important struc- tural polymer of yeast and fungal cell walls. The synthesis of this polymer is achieved by the catalytic action of beta(1,3)-D- glucan synthase (EC 2.4.1.34). Uridine diphosphate (UDP)- [a] A. F. Pheiro, Arist  oteles G oesNeto, Braz Tavares da HoraJ  unior, M. S. J  unior, S. d. Assis Health Department, Enzymology and Fermentation Technology Laboratory, State University of Feira de Santana (UEFS), Universit  aria Boulevard-Km 03, BR 116-BA, Feira de Santana, BA-Brazil, 44031-460 [b] A. G. Taranto Bioinformatics Laboratory, Federal University of Sa˜o Joa˜o Del-Rei (UFSJ), Sebastia˜oGonc ¸alves Coelho Street, 400, Centro Oeste Dona Lindu Campus, Chanadour, Divin opolis, MG-Brazil, 35501-296 E-mail: farmacotony@hotmail.com [c] A. A. Duarte Biomarker v3 Laboratory, State University of Feira de Santana (UEFS), Universit  aria Boulevard-Km 03, BR 116-BA, Feira de Santana, BA-Brazil, 44031-460 [d] Gonc ¸alo Amarante Guimara˜esPereira Biology Institute, State University of Campinas (UNICAMP), Zeferino Vaz University City, 6109, Campinas, SP-Brazil, 23083-970 V C 2012 Wiley Periodicals, Inc. International Journal of Quantum Chemistry 2012, DOI: 10.1002/qua.24212 1 WWW.Q-CHEM.ORG FULL PAPER