240 Current Drug Targets, 2009, 10, 240-245 1389-4501/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd. Genomic Databases and the Search of Protein Targets for Protozoan Parasites Luís Fernando S.M. Timmers 1 , Ivani Pauli 1 , Guy Barros Barcellos 1 , Kelen Beiestorf Rocha 1 , Rafael Andrade Caceres 1,2 , Walter Filgueira de Azevedo Jr. 1,2 and Milena Botelho Pereira Soares 3,4, * 1 Faculdade de Biociências, Laboratório de Bioquímica Estrutural, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre – RS, Brazil; 2 Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universi- dade Católica do Rio Grande do Sul, Porto Alegre – RS, Brazil; 3 Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz. Rua Waldemar Falcão, 121. Candeal 40296-710 - Salvador, BA – Brazil; 4 Hospital São Rafael. Av. São Rafael, 2152. São Marcos 41253-190 - Salvador, BA, Brazil Abstract: The development of databases devoted to biological information opened the possibility to integrate, query and analyze biological data obtained from several sources that otherwise would be scattered through the web. Several issues arise in the handling of biological information, mainly due to the diversity of biological subject matter and the complexity of biological approaches towards phenomena of the living world. The integration of genomic data, three-dimensional structures of proteins, biological activity, and drugs availability allows a system approach to the study of the biology. Here we review the current status of these research efforts to develop genomic databases for protozoan parasites, such as the apicomplexan parasites, Trypanosoma cruzi and Leishmania spp. These databases may help in the discovery and devel- opment of new drugs against parasite-mediated diseases. Key Words: Databases, genomes, protozoan parasites, apicomplexa, Cryptosporidium parvum, Plasmodium falciparum, Leishmania spp., Toxoplasma gondii, Trypanosoma cruzi. INTRODUCTION Protozoan parasites compose a very diverse group of unicellular organisms of the kingdom Protista, some of which have evolved to parasitize humans. The study of para- site biology has attracted attention not only because they are fascinating organisms, but also due to the need of finding tools and developing therapeutic strategies and vaccines, still in great need due to the remarkable social and economic burden they cause on human societies, especially in tropical and subtropical regions of the world [1]. To understand how pathogens infect and survive within their hosts is crucial to identify potential therapeutic targets for parasite-mediated diseases. Drugs can be designed to target and inhibit the function of proteins involved in specific pathways, e.g. shikimate pathway [2-14], purine pathway [15-30], or specific protein targets such as Cyclin-Dependent Kinases [31]. Several metabolic pathways of pivotal importance for the parasites have been proven drug targets for many years. One of the most studied enzymes is Purine Nucleoside Phosphorylase (PNP; EC 2.4.2.1), which participates in de novo synthesis, salvage and interconversion of purines and pyrimidines [32]. The purine salvage pathway is the only possible way for api- complexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites *Address correspondence to this author at the Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz. Rua Waldemar Falcão, 121. Candeal 40296-710 - Salvador, BA – Brazil; E-mail: milena@bahia.fiocruz.br an attractive target for drug development against diseases, such as malaria [32]. PNP catalyzes the reversible phosphorolysis of nucleo- sides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. PNP from Plasmodium falciparum had its crystallographic structure elucidated, which opened the possibility to use this structural information to guide virtual screening initiatives. The structure of PNP from P. falciparum (PfPNP) in complex with 3,4-Dihydroxy-2-[(methylsulfanyl)methyl]-5- (4-oxo-4,5-dihydro-3H-pyrrolo[3,2-D] pyrimidin-7-YL) pyr- rolidinium (MTI) is shown in Fig. (1A) and Fig. (1B) pre- sents the active binding site of the PfPNP:MTI. Analysis of the available genomic databases for Crypto- sporidium parvum, Leishmania braziliensis, Toxoplasma gondii, Trypanosoma cruzi indicates the presence of this enzyme in other genomes, therefore molecular modeling initiatives may generate reliable model for these PNPs, and use this model for structure-based virtual screening initia- tives. The need to understand protein networks has become evident in the so-called "post-genomic Era", due to the ex- plosion in biological and chemical knowledge resulting of genomes sequencing. There is simply too much data (im- ages, models, three-dimensional structures and sequences) available from too many sources [2]. This information may be used to identify potential protein targets in a sequenced