Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus

Andrei S. Halavaty; Rebecca L. Rich; Chao Chen; Jeong Chan Joo; George Minasov; Ievgeniia Dubrovska; James R. Winsor; David G. Myszka; Mark Duban; Ludmilla Shuvalova; Alexander F. Yakunin; Wayne F. Anderson

doi:10.1107/S1399004715004228

Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus

Andrei S. Halavaty, Rebecca L. Rich, Chao Chen, Jeong Chan Joo, George Minasov, Ievgeniia Dubrovska, James R. Winsor, David G. Myszka, Mark Duban, Ludmilla Shuvalova, Alexander F. Yakunin, Wayne F. Anderson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1159-1175
Number of pages	17
Journal	Acta Crystallographica Section D: Biological Crystallography
Volume	71
DOIs	https://doi.org/10.1107/S1399004715004228
State	Published - May 1 2015

Keywords

Staphylococcus aureus
betaine aldehyde dehydrogenase
high-throughput approach
infectious diseases
structural genomics

ASJC Scopus subject areas

Structural Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1107/S1399004715004228

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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. (2015). Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus. Acta Crystallographica Section D: Biological Crystallography, 71, 1159-1175. https://doi.org/10.1107/S1399004715004228

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title = "Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus",

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.",

keywords = "Staphylococcus aureus, betaine aldehyde dehydrogenase, high-throughput approach, infectious diseases, structural genomics",

author = "Halavaty, {Andrei S.} and Rich, {Rebecca L.} and Chao Chen and Joo, {Jeong Chan} and George Minasov and Ievgeniia Dubrovska and Winsor, {James R.} and Myszka, {David G.} and Mark Duban and Ludmilla Shuvalova and Yakunin, {Alexander F.} and Anderson, {Wayne F.}",

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doi = "10.1107/S1399004715004228",

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Halavaty, AS, Rich, RL, Chen, C, Joo, JC, Minasov, G, Dubrovska, I, Winsor, JR, Myszka, DG, Duban, M, Shuvalova, L, Yakunin, AF & Anderson, WF 2015, 'Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus', Acta Crystallographica Section D: Biological Crystallography, vol. 71, pp. 1159-1175. https://doi.org/10.1107/S1399004715004228

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T1 - Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus

AU - Halavaty, Andrei S.

AU - Rich, Rebecca L.

AU - Chen, Chao

AU - Joo, Jeong Chan

AU - Minasov, George

AU - Dubrovska, Ievgeniia

AU - Winsor, James R.

AU - Myszka, David G.

AU - Duban, Mark

AU - Shuvalova, Ludmilla

AU - Yakunin, Alexander F.

AU - Anderson, Wayne F.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

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JF - Acta Crystallographica Section D: Biological Crystallography

ER -

Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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1.90 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus in complex with NAD+ and BME-free Cys289

2.60 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) H448F/Y450L double mutant from Staphylococcus aureus in complex with NAD+ and BME-free Cys289

1.85 Angstrom resolution crystal structure of apo betaine aldehyde dehydrogenase (betB) G234S mutant from Staphylococcus aureus (IDP00699) with BME-free sulfinic acid form of Cys289

Cite this

Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Datasets

1.90 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus in complex with NAD+ and BME-free Cys289

2.60 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) H448F/Y450L double mutant from Staphylococcus aureus in complex with NAD+ and BME-free Cys289

1.85 Angstrom resolution crystal structure of apo betaine aldehyde dehydrogenase (betB) G234S mutant from Staphylococcus aureus (IDP00699) with BME-free sulfinic acid form of Cys289

Cite this