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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Protein thermal denaturation is modulated by central residues in the protein structure network

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Autor(es):
Souza, Valquiria P. [1] ; Ikegami, Cecilia M. [1] ; Arantes, Guilherme M. [1] ; Marana, Sandro R. [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, CP 26077, BR-05513970 Sao Paulo, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: FEBS Journal; v. 283, n. 6, p. 1124-1138, MAR 2016.
Citações Web of Science: 10
Resumo

Network structural analysis, known as residue interaction networks or graphs (RIN or RIG, respectively) or protein structural networks or graphs (PSN or PSG, respectively), comprises a useful tool for detecting important residues for protein function, stability, folding and allostery. In RIN, the tertiary structure is represented by a network in which residues (nodes) are connected by interactions (edges). Such structural networks have consistently presented a few central residues that are important for shortening the pathways linking any two residues in a protein structure. To experimentally demonstrate that central residues effectively participate in protein properties, mutations were directed to seven central residues of the beta-glucosidase Sf beta gly (beta-D-glucoside glucohydrolase; EC 3.2.1.21). These mutations reduced the thermal stability of the enzyme, as evaluated by changes in transition temperature (T-m) and the denaturation rate at 45 degrees C. Moreover, mutations directed to the vicinity of a central residue also caused significant decreases in the T-m of Sf beta gly and clearly increased the unfolding rate constant at 45 degrees C. However, mutations at noncentral residues or at surrounding residues did not affect the thermal stability of Sf beta gly. Therefore, the data reported in the present study suggest that the perturbation of the central residues reduced the stability of the native structure of Sf beta gly. These results are in agreement with previous findings showing that networks are robust, whereas attacks on central nodes cause network failure. Finally, the present study demonstrates that central residues underlie the functional properties of proteins. (AU)

Processo FAPESP: 14/19439-5 - Redes estruturais e propriedades funcionais em enzimas
Beneficiário:Sandro Roberto Marana
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/55914-9 - (bioen/pronex FAPESP) Development of beta-glycosidases designed to improve the efficiency of noncomplexed cellulase systems
Beneficiário:Sandro Roberto Marana
Linha de fomento: Auxílio à Pesquisa - Programa BIOEN - Temático
Processo FAPESP: 14/21900-2 - Desenvolvimento e aplicação de simulação computacional e análise espectroscópica para o estudo de metaloenzimas e de proteínas flexíveis
Beneficiário:Guilherme Menegon Arantes
Linha de fomento: Auxílio à Pesquisa - Regular