Análise de resíduos conservados e correlacionados das cisteíno proteases

• Ano de defesa: 2019
• Autor(a) principal: Bárbara Monteiro de Castro Ataíde
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Bioquímica e Imunologia; UFMG
• Palavras-chave em Português: Cisteíno proteases; Cruzaína; Alinhamento múltiplo de sequências; Correlação; Coevolução; Bioquímica; Cisteína Proteases; Alinhamento de Sequência; Coevolução Biológica
• Link de acesso: http://hdl.handle.net/1843/30908

Proteins evolve over time, due to the accumulation of mutations, insertions and deletions in the genes that encode them. Highly conserved positions generally refer to residues that are strictly necessary for the structure of the protein or for its function. The DRCN (Decomposition of Residue Coevolution Networks) methodology allows the study of coevolution of residues in protein families. To do this, it consists of five basic steps: filtering the alignment, calculating correlations, decomposing the network, generating auxiliary visualization files and annotating positions by automatic search in UniProt. Cysteine proteases are a large and diverse group of enzymes belonging to the CA clan and the C1 family (papain family) and can be found in all animals and plant kingdoms as well as in many viruses and prokaryotes. The present work aims to analyze and discuss the importance of correlated and conserved residues of the cysteine protease family from the multiple sequence alignment. For this, we use the PFSTATS software, which employs the DRCN methodology. There were 34 correlated residues found in 5 coevoluted communities. Community 1 is the largest community, consisting of 22 residues coevolved by structural issues, such as Cys22 and Cys63 and Cys56 and Cys101, which carry disulfide bridges; as well as for functional issues, such as Pro2, Phe28, Gly35 and Tyr89, which are located in predicted allosteric sites of cruzain. Community 2 is composed of 6 residues, among them residues of the catalytic dyad, Cys25 and His162, and residues Gly23 and Gly65, which coevolve for structural reasons. Communities 3, 4 and 5 have only 2 residues each. The Cys155 residue of community 3 has structural importance, as well as residues Val13 and Lys181 (community 4) and Gln51 (community 5). The residues of community 5, Leu48 and Gln51 have functional importance and the residue Ser55 (community 3) still does not present its function described in the literature. Also 10 residues were found that are highly conserved evolutionarily in this family. While some residues, including those that make up the catalytic dyad (Cys25 and His162), are conserved for functional reasons, others are for structural reasons (Ser49, Gly168, Gly189 and Gly192).