Force-induced chemical reactions on the metal centre in a single metalloprotein molecule

Autor(es)

Zheng, Peng ^{[1, 2]} ; Arantes, Guilherme M. ^[3] ; Field, Martin J. ^[4] ; Li, Hongbin ^[1]

Afiliação do(s) autor(es)

^[1] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1 - Canada

^[2] Nanjing Univ, Sch Chem & Chem Engn, Nanjing 210063, Jiangsu - Peoples R China

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508900 Sao Paulo, SP - Brazil

^[4] Univ Grenoble 1, CEA CNRS, IBS Jean Pierre Ebel, F-38044 Grenoble 9 - France

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 6, JUN 2015.
• Citações Web of Science: 15

Resumo

Metalloproteins play indispensable roles in biology owing to the versatile chemical reactivity of metal centres. However, studying their reactivity in many metalloproteins is challenging, as protein three-dimensional structure encloses labile metal centres, thus limiting their access to reactants and impeding direct measurements. Here we demonstrate the use of singlemolecule atomic force microscopy to induce partial unfolding to expose metal centres in metalloproteins to aqueous solution, thus allowing for studying their chemical reactivity in aqueous solution for the first time. As a proof-of-principle, we demonstrate two chemical reactions for the FeS4 centre in rubredoxin: electrophilic protonation and nucleophilic ligand substitution. Our results show that protonation and ligand substitution result in mechanical destabilization of the FeS4 centre. Quantum chemical calculations corroborated experimental results and revealed detailed reaction mechanisms. We anticipate that this novel approach will provide insights into chemical reactivity of metal centres in metalloproteins under biologically more relevant conditions. (AU)

• 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/02501-4 - Simulação computacional e análise espectroscópica de proteínas envolvidas em bioenergética e em reconhecimento molecular
• Beneficiário: Guilherme Menegon Arantes
• Modalidade de apoio: Auxílio à Pesquisa - Regular