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Title: Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus

Journal Article · · Acta Crystallographica. Section D: Biological Crystallography (Online)
 [1];  [2];  [3];  [3];  [1];  [1];  [1];  [2];  [4];  [1];  [3];  [1]
  1. Northwestern Univ., Chicago, IL (United States). Dept. of Biochemistry and Molecular Genetics; Center for Structural Genomics of Infectious Diseases (CSGID), Chicago, IL (United States)
  2. Biosensor Tools LLC, Salt Lake City, UT (United States)
  3. Univ. of Toronto, ON (Canada). Dept. of Chemical Engineering and Applied Chemistry
  4. Center for Structural Genomics of Infectious Diseases (CSGID), Chicago, IL (United States)

When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus (MRSA) restores its growth and establishes a new steady state by accumulating the osmoprotectant metabolite betaine. Effective osmoregulation has also been implicated in the acquirement of a profound antibiotic resistance by MRSA. Betaine can be obtained from the bacterial habitat or produced intracellularly from choline via the toxic betaine aldehyde (BA) employing the choline dehydrogenase and betaine aldehyde dehydrogenase (BADH) enzymes. Here, it is shown that the putative betaine aldehyde dehydrogenase SACOL2628 from the early MRSA isolate COL ( SaBADH) utilizes betaine aldehyde as the primary substrate and nicotinamide adenine dinucleotide (NAD+) as the cofactor. Surface plasmon resonance experiments revealed that the affinity of NAD+, NADH and BA for SaBADH is affected by temperature, pH and buffer composition. Finally, five crystal structures of the wild type and three structures of the Gly234Ser mutant of SaBADH in the apo and holo forms provide details of the molecular mechanisms of activity and substrate specificity/inhibition of this enzyme.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357; 085P1000817; HHSN272200700058C; HHSN272201200026C
OSTI ID:
1233329
Journal Information:
Acta Crystallographica. Section D: Biological Crystallography (Online), Vol. 71, Issue 5; ISSN 1399-0047
Publisher:
International Union of CrystallographyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

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