Busca avançada
Ano de início
Entree
(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.)

Mutations close to a hub residue affect the distant active site of a GH1 beta-glucosidase

Texto completo
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, Sao Paulo, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 13, n. 6 JUN 6 2018.
Citações Web of Science: 1
Resumo

The tertiary structure of proteins has been represented as a network, in which residues are nodes and their contacts are edges. Protein structure networks contain residues, called hubs or central, which are essential to form short connection pathways between any pair of nodes. Hence hub residues may effectively spread structural perturbations through the protein. To test whether modifications nearby to hub residues could affect the enzyme active site, mutations were introduced in the beta-glycosidase Sf beta gly (PDB-ID: 5CGO) directed to residues that form an a-helix (260-265) and a beta-strand (335-337) close to one of its main hub residues, F251, which is approximately 14 angstrom from the Sf beta gly active site. Replacement of residues A263 and A264, which side-chains project from the alpha-helix towards F251, decreased the rate of substrate hydrolysis. Mutation A263F was shown to weaken noncovalent interactions involved in transition state stabilization within the Sf beta gly active site. Mutations placed on the opposite side of the same alpha-helix did not show these effects. Consistently, replacement of V336, which side-chain protrudes from a beta-strand face towards F251, inactivated Sf beta gly. Next to V336, mutation S337F also caused a decrease in noncovalent interactions involved in transition state stabilization. Therefore, we suggest that mutations A263F, A264F, V336F and S337F may directly perturb the position of the hub F251, which could propagate these perturbations into the Sf beta gly active site through short connection pathways along the protein network. (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: 16/22365-9 - Redes estruturais e dinâmica em enzimas
Beneficiário:Sandro Roberto Marana
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/57619-4 - Bases moleculares das propriedades catalíticas das enzimas
Beneficiário:Sandro Roberto Marana
Linha de fomento: Auxílio à Pesquisa - Regular