| Texto completo | |
| Autor(es): |
Rossini, Nicolas de Oliveira
;
Silva, Catharina
;
Dias, Marcio Vinicius Bertacine
Número total de Autores: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Structural Biology; v. 215, n. 2, p. 10-pg., 2023-03-23. |
| Resumo | |
The cytoplasmatic biosynthesis of the stem peptide from the peptidoglycan in bacteria involves six steps, which have the role of three ATP-dependent Mur ligases that incorporate three consecutive amino acids to a substrate precursor. MurE is the last Mur ligase to incorporate a free amino acid. Although the structure of MurE from Mycobacterium tuberculosis (MtbMurE) was determined at 3.0 angstrom, the binding mode of meso-Diaminopimelate (m -DAP) and the effect of substrate absence is unknown. Herein, we show the structure of MurE from M. thermoresistibile (MthMurE) in complex with ADP and m-DAP at 1.4 angstrom resolution. The analysis of the structure indicates key conformational changes that the substrate UDP-MurNAc-L-Ala-D-Glu (UAG) and the free amino acid m-DAP cause on the MthMurE conformation. We observed several movements of domains or loop regions that displace their position in order to perform enzymatic catalysis. Since MthMurE has a high similarity to MtbMurE, this enzyme could also guide strategies for structure-based antimicrobial discovery to fight against tuberculosis or other mycobacterial infections. (AU) | |
| Processo FAPESP: | 16/18721-4 - Bases estruturais do controle da elongação e da divisão celular em Mycobacterium tuberculosis e identificação de novos hits a fármacos baseado em triagem de fragmentos |
| Beneficiário: | Catharina dos Santos Silva |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 19/17037-0 - Identificação de compostos que interagem com a MurE de Mycobacterium tuberculosis através da triagem de fragmentos |
| Beneficiário: | Nicolas de Oliveira Rossini |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 20/03850-9 - Parede celular micobacteriana: estudo estrutural e estratégias de inibição de enzimas relacionadas com sua biossíntese e regulação |
| Beneficiário: | Marcio Vinicius Bertacine Dias |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |