4QTO

1.65 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus with BME-modified Cys289 and PEG molecule in active site

Summary for 4QTO

• Entry DOI: 10.2210/pdb4qto/pdb
• Related: 4MPB 4MPY 4NEA 4NU9 4Q92 4QJE 4QN2
• Descriptor: Betaine aldehyde dehydrogenase, SODIUM ION, TRIETHYLENE GLYCOL, ... (8 entities in total)
• Functional Keywords: betb, structural genomics, nad, niaid, national institute of allergy and infectious diseases, csgid, rossmann fold, center for structural genomics of infectious diseases, oxidoreductase
• Biological source: Staphylococcus aureus subsp. aureus COL
• Total number of polymer chains: 4
• Total formula weight: 231998.45

Authors

Halavaty, A.S.,Minasov, G.,Dubrovska, I.,Winsor, J.,Shuvalova, L.,Anderson, W.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2014-07-08, release date: 2014-07-16, Last modification date: 2024-11-20)

Primary citation

Halavaty, A.S.,Rich, R.L.,Chen, C.,Joo, J.C.,Minasov, G.,Dubrovska, I.,Winsor, J.R.,Myszka, D.G.,Duban, M.,Shuvalova, L.,Yakunin, A.F.,Anderson, W.F.
Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus.
Acta Crystallogr.,Sect.D, 71:1159-1175, 2015

PubMed Abstract: 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. 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.

PubMed: 25945581
DOI: 10.1107/S1399004715004228

Experimental method

X-RAY DIFFRACTION (1.65 Å)