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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Souza, Valquiria P. [1] ; Ikegami, Cecilia M. [1] ; Arantes, Guilherme M. [1] ; Marana, Sandro R. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, CP 26077, BR-05513970 Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: FEBS Journal; v. 283, n. 6, p. 1124-1138, MAR 2016.
Web of Science Citations: 9
Abstract

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)

FAPESP's process: 14/21900-2 - Development and application of computer simulation and spectroscopical analysis to study metalloenzymes and flexible proteins
Grantee:Guilherme Menegon Arantes
Support Opportunities: Regular Research Grants
FAPESP's process: 08/55914-9 - Development of beta-glycosidases designed to improve the efficiency of noncomplexed cellulase systems
Grantee:Sandro Roberto Marana
Support Opportunities: Program for Research on Bioenergy (BIOEN) - Thematic Grants
FAPESP's process: 14/19439-5 - Structural networks and functional properties in enzymes
Grantee:Sandro Roberto Marana
Support Opportunities: Regular Research Grants