Volume 75, Issue 6 pp. 419-427
research communications

Cruzain structures: apocruzain and cruzain bound to S-methyl thiomethanesulfonate and implications for drug design

Elany Barbosa da Silva

Elany Barbosa da Silva

Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

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Elfriede Dall

Elfriede Dall

Department of Biosciences, University of Salzburg, Salzburg, Austria

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Peter Briza

Peter Briza

Department of Biosciences, University of Salzburg, Salzburg, Austria

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Hans Brandstetter

Hans Brandstetter

Department of Biosciences, University of Salzburg, Salzburg, Austria

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Rafaela Salgado Ferreira

Corresponding Author

Rafaela Salgado Ferreira

Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Rafaela Salgado Ferreira, e-mail: [email protected]Search for more papers by this author
First published: 17 June 2019

Abstract

Chagas disease, which is caused by Trypanosoma cruzi, affects more than six million people worldwide. Cruzain is the major cysteine protease involved in the survival of this parasite. Here, the expression, purification and crystallization of this enzyme are reported. The cruzain crystals diffracted to 1.2 Å resolution, yielding two novel cruzain structures: apocruzain and cruzain bound to the reversible covalent inhibitor S-methyl thiomethanesulfonate. Mass-spectrometric experiments confirmed the presence of a methylthiol group attached to the catalytic cysteine. Comparison of these structures with previously published structures indicates the rigidity of the cruzain structure. These results provide further structural information about the enzyme and may help in new in silico studies to identify or optimize novel prototypes of cruzain inhibitors.

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