Crystal structure of betaine aldehyde dehydrogenase from Burkholderia pseudomallei
Dylan K. Beard, Sandhya Subramanian, Jan Abendroth, Thomas E. Edwards, Peter J. Myler, and Oluwatoyin A. Asojo [1]
Molecular Tour
Burkholderia pseudomallei is a rod-shaped, motile, flagellated, soil-dwelling gram-negative proteobacterium of the Burkholderiaceae family that thrives in tropical and subtropical regions. B. pseudomallei causes melioidosis, a deadly emerging opportunistic infection mainly of the immunocompromised. B. pseudomallei is transmitted through open wounds, contact with contaminated soil and water, ingestion, or inhalation, and is also a potential biological warfare agent. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) has determined and solved X-ray structures of a potential drug target betaine aldehyde dehydrogenase (BADH) from B. pseudomallei (BpBADH):
- , colored in rainbow from blue (N-terminus) to red (C-terminus); 6wsa.
- , monomers are shown as green and cyan ribbons, with NAD shown as ball-and-sticks; 6wsb.
The structures are similar to those of BADH from Pseudomonas aeruginosa (PaBADH):
PaBADH is inhibited by the drug disulfiram which is an approved drug. Our preliminary analysis could facilitate drug repurposing studies for melioidosis. This project is an educational collaboration between the SSGCID and Hampton University. The SSGCID consortium is directed by Dr. Peter Myler (principal investigator) and comprises many different scientists working at multiple centers towards determining the three-dimensional structures of proteins from biodefense organisms and emerging infectious diseases. Dylan K. Beard was part of a pilot Hampton University Chemistry Education and Mentorship Course-based undergraduate research (HU-ChEM CURES) funded by the NIGMS.
References
- ↑ Beard DK, Subramanian S, Abendroth J, Dranow DM, Edwards TE, Myler PJ, Asojo OA. Crystal structure of betaine aldehyde dehydrogenase from Burkholderia pseudomallei. Acta Crystallogr F Struct Biol Commun. 2022 Feb 1;78(Pt 2):45-51. doi:, 10.1107/S2053230X21013455. Epub 2022 Jan 27. PMID:35102892 doi:http://dx.doi.org/10.1107/S2053230X21013455
