Structure of Urocanate Hydratase from the protozoan Trypanosoma cruzi

Autor(es)

Boreiko, Sheila ^[1] ; Silva, Marcio ^[2] ; Melo, Raissa de F. P. ^[3] ; Silber, Ariel M. ^[3] ; Iulek, Jorge ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Ponta Grossa, Dept Chem, BR-84030900 Ponta Grossa, PR - Brazil

^[2] Fed Technol Univ Parana, Dept Educ, BR-84016210 Ponta Grossa, PR - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Biochem Tryps, LaBTryps, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 146, p. 716-724, MAR 1 2020.
• Citações Web of Science: 0

Resumo

The enzyme Urocanate Hydratase (UH) participates in the catabolic pathway of L-histidine. Trypanosoma cruzi Urocanate Hydratase (TcUH) is identified as a therapeutic molecular target in the WHO/TDR Targets Database. We report the 3D structure determination and number of features of TcUH, and compared it to other few available bacterial UH structures. Each monomer presents two domains and one NAD(+) molecule. Superpositions revealed differences in the relative orientation of domains within monomers, such that TcUH monomer A resembles Urocanate Hydratase from Geobacillus kaustophilus (GkUH) (open conformation), while monomer C resembles Urocanate Hydratase from Pseudomonas putida (PpUH) and Urocanate Hydratase from Bacillus subtilis (BsUH) (closed conformations). We use the structure of TcUH to make considerations about 3 non-deleterious and 2 deleterious mutations found in human UHs: non-deleterious mutations could be accommodated without large displacements or interaction interruptions, whereas deleterious mutations in one case might disrupt an alpha-helix (as previously suggested) and in the other case, besides disrupting the enzyme interaction with the substrate, might interfere with interdomain movement. (C) 2019 Published by Elsevier B.V. (AU)

• Processo FAPESP: 08/57910-0 - Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas - INBEQMeDI
• Beneficiário: Richard Charles Garratt
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/06034-2 - O papel biológico de aminoácidos e seus metabólitos derivados em Trypanosoma cruzi
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Temático