| Texto completo | |
| Autor(es): |
Begum, Afshan
;
Drebes, Julia
;
Kikhney, Alexey
;
Mueller, Ingrid B.
;
Perbandt, Markus
;
Svergun, Dmitri
;
Wrenger, Carsten
;
Betzel, Christian
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY; v. 69, p. 10-pg., 2013-12-01. |
| Resumo | |
Staphylococcus aureus TenA (SaTenA) is a thiaminase type II enzyme that catalyzes the deamination of aminopyrimidine, as well as the cleavage of thiamine into 4-amino-5-hydroxymethyl- 2-methylpyrimidine (HMP) and 5-(2-hydroxyethyl)4-methylthiazole (THZ), within thiamine (vitamin B-1) metabolism. Further, by analogy with studies of Bacillus subtilis TenA, SaTenA may act as a regulator controlling the secretion of extracellular proteases such as the subtilisin type of enzymes in bacteria. Thiamine biosynthesis has been identified as a potential drug target of the multi-resistant pathogen S. aureus and therefore all enzymes involved in the S. aureus thiamine pathway are presently being investigated in detail. Here, the structure of SaTenA, determined by molecular replacement and refined at 2.7 angstrom resolution to an R factor of 21.6% with one homotetramer in the asymmetric unit in the orthorhombic space group P2(1)2(1)2(1), is presented. The tetrameric state of wild-type (WT) SaTenA was postulated to be the functional biological unit and was confirmed by small-angle X-ray scattering (SAXS) experiments in solution. To obtain insights into structural and functional features of the oligomeric SaTenA, comparative kinetic investigations as well as experiments analyzing the structural stability of the WT SaTenA tetramer versus a monomeric SaTenA mutant were performed. (AU) | |
| Processo FAPESP: | 09/54325-2 - Elucidation of vitamin B metabolism in the human malaria parasite Plasmodium falciparum and their validation as a target for chemotherapy |
| Beneficiário: | Carsten Wrenger |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |