RESUMEN
Burkholderia pseudomallei infection causes melioidosis, which is often fatal if untreated. There is a need to develop new and more effective treatments for melioidosis. This study reports apo and cofactor-bound crystal structures of the potential drug target betaine aldehyde dehydrogenase (BADH) from B. pseudomallei. A structural comparison identified similarities to BADH from Pseudomonas aeruginosa which is inhibited by the drug disulfiram. This preliminary analysis could facilitate drug-repurposing studies for B. pseudomallei.
Asunto(s)
Proteínas Bacterianas/química , Betaína Aldehído Deshidrogenasa/química , Burkholderia pseudomallei/enzimología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Betaína Aldehído Deshidrogenasa/genética , Betaína Aldehído Deshidrogenasa/metabolismo , Cristalografía por Rayos X , Modelos Moleculares , Conformación Proteica , Pseudomonas aeruginosa/enzimologíaRESUMEN
The name of one of the authors in Beard et al. [(2022), Acta Cryst. F78, 59-65] is corrected.
RESUMEN
Giardiasis is the most prevalent diarrheal disease globally and affects humans and animals. It is a significant problem in developing countries, the number one cause of travelers' diarrhea and affects children and immunocompromised individuals, especially HIV-infected individuals. Giardiasis is treated with antibiotics (tinidazole and metronidazole) that are also used for other infections such as trichomoniasis. The ongoing search for new therapeutics for giardiasis includes characterizing the structure and function of proteins from the causative protozoan Giardia lamblia. These proteins include hypothetical proteins that share 30% sequence identity or less with proteins of known structure. Here, the atomic resolution structure of a 15.6â kDa protein was determined by molecular replacement. The structure has the two-layer αß-sandwich topology observed in the prototypical endoribonucleases L-PSPs (liver perchloric acid-soluble proteins) with conserved allosteric active sites containing small molecules from the crystallization solution. This article is an educational collaboration between Hampton University and the Seattle Structural Genomics Center for Infectious Disease.