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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. 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.

Authors:
 [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)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1233329
Grant/Contract Number:  
AC02-06CH11357; 085P1000817; HHSN272200700058C; HHSN272201200026C
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography (Online)
Additional Journal Information:
Journal Volume: 71; Journal Issue: 5; Journal ID: ISSN 1399-0047
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; betaine aldehyde dehydrogenase; Staphylococcus aureus; structural genomics; high-throughput approach; infectious diseases

Citation Formats

Halavaty, Andrei S., Rich, Rebecca L., Chen, Chao, Joo, Jeong Chan, Minasov, George, Dubrovska, Ievgeniia, Winsor, James R., Myszka, David G., Duban, Mark, Shuvalova, Ludmilla, Yakunin, Alexander F., and Anderson, Wayne F. Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus. United States: N. p., 2015. Web. doi:10.1107/S1399004715004228.
Halavaty, Andrei S., Rich, Rebecca L., Chen, Chao, Joo, Jeong Chan, Minasov, George, Dubrovska, Ievgeniia, Winsor, James R., Myszka, David G., Duban, Mark, Shuvalova, Ludmilla, Yakunin, Alexander F., & Anderson, Wayne F. Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus. United States. https://doi.org/10.1107/S1399004715004228
Halavaty, Andrei S., Rich, Rebecca L., Chen, Chao, Joo, Jeong Chan, Minasov, George, Dubrovska, Ievgeniia, Winsor, James R., Myszka, David G., Duban, Mark, Shuvalova, Ludmilla, Yakunin, Alexander F., and Anderson, Wayne F. 2015. "Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus". United States. https://doi.org/10.1107/S1399004715004228. https://www.osti.gov/servlets/purl/1233329.
@article{osti_1233329,
title = {Structural and functional analysis of betaine aldehyde dehydrogenase from Staphylococcus aureus},
author = {Halavaty, Andrei S. and Rich, Rebecca L. and Chen, Chao and Joo, Jeong Chan and Minasov, George and Dubrovska, Ievgeniia and Winsor, James R. and Myszka, David G. and Duban, Mark and Shuvalova, Ludmilla and Yakunin, Alexander F. and Anderson, Wayne F.},
abstractNote = {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.},
doi = {10.1107/S1399004715004228},
url = {https://www.osti.gov/biblio/1233329}, journal = {Acta Crystallographica. Section D: Biological Crystallography (Online)},
issn = {1399-0047},
number = 5,
volume = 71,
place = {United States},
year = {Sat Apr 25 00:00:00 EDT 2015},
month = {Sat Apr 25 00:00:00 EDT 2015}
}

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Cited by: 15 works
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Works referenced in this record:

Steady-state kinetic mechanism of the NADP+- and NAD+-dependent reactions catalysed by betaine aldehyde dehydrogenase from Pseudomonas aeruginosa
journal, December 2000


Overview of the CCP 4 suite and current developments
journal, March 2011


Dali server: conservation mapping in 3D
journal, May 2010


Methicillin-Resistant Staphylococcus aureus : A Food-Borne Pathogen?
journal, February 2013


Clonal Comparison of Staphylococcus aureus Isolates from Healthy Pig Farmers, Human Controls, and Pigs
journal, May 2005


MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
text, January 2007


Induction of the mar operon by miscellaneous groceries
journal, November 2004


Potential monovalent cation-binding sites in aldehyde dehydrogenases
journal, February 2013


MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
journal, May 2007


Betaine in human nutrition
journal, September 2004


Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server
journal, December 2013


Structure of the Type III Secretion Effector Protein ExoU in Complex with Its Chaperone SpcU
journal, November 2012


Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007


LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery
journal, October 2011


Structure-Based Mutational Studies of Substrate Inhibition of Betaine Aldehyde Dehydrogenase BetB from Staphylococcus aureus
journal, April 2014


DaliLite workbench for protein structure comparison
journal, June 2000


Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era
journal, September 2009


"Celbenin" - resistant Staphylococci
journal, January 1961


Environmental Stress and Antibiotic Resistance in Food-Related Pathogens
journal, December 2006


Genes for the synthesis of the osmoprotectant glycine betaine from choline in the moderately halophilic bacterium Halomonas elongata DSM 3043
journal, February 2000


Purification and characterization of osmoregulatory betaine aldehyde dehydrogenase of Escherichiacoli
journal, June 1990


Amino Acid Residues Critical for the Specificity for Betaine Aldehyde of the Plant ALDH10 Isoenzyme Involved in the Synthesis of Glycine Betaine
journal, February 2012


Very fast prediction and rationalization of pKa values for protein-ligand complexes
journal, May 2008


Choline transport activity in Staphylococcus aureus induced by osmotic stress and low phosphate concentrations.
journal, January 1993


Osmoadaptation in bacteria and archaea: common principles and differences
journal, December 2001


HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes
journal, July 2006


MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009


Coot model-building tools for molecular graphics
journal, November 2004


Role for Glycine Betaine Transport in Vibrio cholerae Osmoadaptation and Biofilm Formation within Microbial Communities
journal, July 2005


TrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential
journal, January 2020


Choline and betaine in health and disease
journal, May 2010


Antimicrobials, drug discovery, and genome mining
journal, December 2012


Identification of a high-affinity glycine betaine transport system in Staphylococcus aureus.
journal, January 1993


The Choline-Converting Pathway inStaphylococcus xylosus C2A: Genetic and Physiological Characterization
journal, April 1999


Purification and properties of betaine aldehyde dehydrogenase from Xanthomonas translucens
journal, January 1992


Optimal description of a protein structure in terms of multiple groups undergoing TLS motion
journal, March 2006


[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997


Disruption of the Coenzyme Binding Site and Dimer Interface Revealed in the Crystal Structure of Mitochondrial Aldehyde Dehydrogenase “Asian” Variant
journal, June 2005


"Celbenin" - resistant Staphylococci
journal, January 1961


Novel NADPH–cysteine covalent adduct found in the active site of an aldehyde dehydrogenase
journal, October 2011


Comparison of Mortality Associated with Methicillin‐Resistant and Methicillin‐Susceptible Staphylococcus aureus Bacteremia: A Meta‐analysis
journal, January 2003


Very fast empirical prediction and rationalization of protein pKa values
journal, October 2005


"Celbenin" - resistant Staphylococci
journal, January 1961


Emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different animal species
journal, February 2010


Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency?
journal, January 2010


Resistance heterogeneity in methicillin-resistant Staphylococcus aureus
journal, May 1984


The oligomeric structures of plant cryptochromes
journal, May 2020


The Antibiotic Pipeline — Challenges, Costs, and Values
journal, August 2004


Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020


Staphylococcus aureus requires cardiolipin for survival under conditions of high salinity
journal, January 2011


PROCHECK: a program to check the stereochemical quality of protein structures
journal, April 1993


MICROBIOLOGY:Deconstructing Vancomycin
journal, April 1999


Kinetic and structural features of betaine aldehyde dehydrogenases: Mechanistic and regulatory implications
journal, January 2010


Characterization of Glycine Betaine Porter I from Listeria monocytogenes and Its Roles in Salt and Chill Tolerance
journal, February 2002


Crystal Structure and Kinetics Identify Escherichia coli YdcW Gene Product as a Medium-chain Aldehyde Dehydrogenase
journal, October 2004


What makes resistance to methicillin heterogeneous?
text, January 2003


Update on the aldehyde dehydrogenase gene (ALDH) superfamily
journal, January 2011


MRSA: the first half century
journal, October 2011


Carriage of Staphylococcus aureus among 104 healthy persons during a 19-month period
journal, August 1995


PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019


What makes resistance to methicillin heterogeneous?
journal, August 2003


Betaine aldehyde dehydrogenase in plants
journal, March 2009


Features and development of Coot
journal, March 2010


Rapid Purification and Properties of Betaine Aldehyde Dehydrogenase from Pseudomonas aeruginosa
journal, February 1999


REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011


Cloning, Expression, and Purification of Choline Dehydrogenase from the Moderate Halophile Halomonas elongata
journal, April 2003


Plant ALDH10 Family: IDENTIFYING CRITICAL RESIDUES FOR SUBSTRATE SPECIFICITY AND TRAPPING A THIOHEMIACETAL INTERMEDIATE
journal, February 2013


Monovalent cations requirements for the stability of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa, porcine kidney and amaranth leaves
journal, February 2003


Staphylococcus colonization of the skin and antimicrobial peptides
journal, April 2010


Overview of the CCP4 suite and current developments.
text, January 2011


Bacterial osmoadaptation: the role of osmolytes in bacterial stress and virulence
journal, March 2002


Coenzyme Isomerization Is Integral to Catalysis in Aldehyde Dehydrogenase ,
journal, June 2003


Structure of betaine aldehyde dehydrogenase at 2.1 Å resolution
journal, October 1998


Phaser crystallographic software
journal, July 2007


Staphylococcus aureus osmoregulation: roles for choline, glycine betaine, proline, and taurine.
journal, January 1992


Livestock-associated Staphylococcus aureus
journal, August 2012


Horse Liver Aldehyde Dehydrogenase
journal, January 1972


Works referencing / citing this record:

Studying NAD(P)H cofactor-binding to alcohol dehydrogenases through global analysis of circular dichroism spectra
journal, January 2019


Structural insights into betaine aldehyde dehydrogenase (BADH2) from Oryza sativa explored by modeling and simulations
journal, August 2018