PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
CCR5 and HIV Infection
January 2015
HIV/AIDS: Pre-fusion Env Exposed
January 2015
HIV/AIDS: Slide to Enter
January 2015
Updating ModBase
January 2015
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Bacterial CDI Toxins
June 2014
Immunity: One Antibody to Rule Them All
June 2014
Virology: A Bat Influenza Hemagglutinin
March 2014
Virology: Making Sensitive Magic
March 2014
Virology: Visualizing Cyanophage Assembly
March 2014
Virology: Zeroing in on HBV Egress
March 2014
March 2014
Cas4 Nuclease and Bacterial Immunity
February 2014
Microbial Pathogenesis: A GNAT from Pseudomonas
February 2014
Microbial Pathogenesis: Targeting Drug Resistance in Mycobacterium tuberculosis
February 2014
Microbiome: The Dynamics of Infection
September 2013
Membrane Proteome: A Funnel-like Viroporin
August 2013
Infectious Diseases: A Pathogen Ubiquitin Ligase
May 2013
Infectious Diseases: A Shared Syringe
May 2013
Infectious Diseases: Determining the Essential Structome
May 2013
Infectious Diseases: Targeting Meningitis
May 2013
NDM-1 and Antibiotics
May 2013
Bacterial Hemophores
January 2013
Microbial Pathogenesis: Computational Epitope Prediction
January 2013
Microbial Pathogenesis: Influenza Inhibitor Screen
January 2013
Microbial Pathogenesis: Measles Virus Attachment
January 2013
Microbial Pathogenesis: NEAT Iron
January 2013
Membrane Proteome: Sphingolipid Synthesis Selectivity
December 2012
A signal sensing switch
September 2012
Gauging needle structure
July 2012
Anthrax Stealth Siderophores
June 2012
A Pseudomonas L-serine dehydrogenase
May 2012
Pilus Assembly Protein TadZ
April 2012
Making Lipopolysaccharide
January 2012
Superbugs and Antibiotic Resistance
December 2011
A change to resistance
November 2011
An effective and cooperative dimer
November 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
Breaking down the defenses
September 2011
Moving some metal
August 2011
Capsid assembly in motion
April 2011
Know thy enemy … structurally
October 2010
Treating sleeping sickness
May 2010
Bacterial spore kinase
April 2010
Hemolysin BL
January 2010
Unusual cell division
October 2009
Anthrax evasion tactics
September 2009
Toxin-antitoxin VapBC-5
September 2009
Antibiotic target
August 2009
July 2009
Tackling influenza
June 2009
You look familiar: the Type VI secretion system
June 2009
Unique SARS
April 2009
Anthrax stealth molecule
March 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Antiviral evasion
October 2008
SARS connections
September 2008
SARS Coronavirus Nonstructural Protein 1
June 2008

Research Themes Infectious diseases

A Pseudomonas L-serine dehydrogenase

SBKB [doi:10.1038/sbkb.2011.77]
Featured Article - May 2012
Short description: Structural studies of an uncharacterized Pseudomonas aeruginosa enzyme reveal a dehydrogenase with a substrate preference for L-serine.

Structure of the PA0743 tetramer, with each chain colored differently. The modeled HEPES is shown in stick representation. Figure courtesy of Alexander Yakunin.

The β-hydroxyacid dehydrogenases constitute a ubiquitous family of enzymes. Some members are involved in central metabolic processes in various organisms, but the vast majority remains uncharacterized.

In a recent report, Yakunin and colleagues (PSI MCSG) performed structural studies on the predicted β-hydroxyisobutyrate dehydrogenase PA0743 from the bacterium Pseudomonas aeruginosa, which encodes six predicted members of the enzyme family. The preferred substrates of affinity-purified PA0743 are L-serine and methyl-DL-serine (not the predicted substrate, 3-hydroxyisobutyrate). The enzyme catalyzes cofactor-dependent oxidation of the substrate hydroxyl acid to a semialdehyde; its preferred cofactor is NAD+, but NADP+ can also be used, although yielding lower activity.

The authors solved the crystal structure of the apoenzyme (PDB 3OBB) to 2.2 Å, revealing a two-domain protein with an N-terminal Rossmann fold domain and a C-terminal all-α domain connected by a long α9 helix. Consistent with gel filtration studies, structural analysis indicated that the enzyme is tetrameric. The researchers observed a weak electron density in the interdomain cleft close to the predicted active site that was modeled as a HEPES molecule, as HEPES was present in the crystallization buffer. They predicted that HEPES binding mimics that of the L-serine or methyl-DL-serine substrate.

The crystal structure of the PA0743-NAD+ complex (PDB 3Q3C) revealed that NAD+ also binds within the interdomain cleft at a non-overlapping site with HEPES. NAD+ binding does not cause major structural rearrangements relative to the apoenzyme. Site-directed mutagenesis confirmed the critical role of the active site lysine, Lys171, and defined additional residues important for NAD+-dependent L-serine dehydrogenase activity.

The biological function of PA0743 in P. aeruginosa remains unclear. While its substrate preference suggests an involvement in serine metabolism, Yakunin and colleagues observed that mutant strains can grow on L-serine as a sole nitrogen source. It is possible that other enzymes may compensate, particularly under laboratory conditions, or PA0743 may be involved in other metabolic processes. Further experiments will be needed to elucidate its biological role, and will doubtless be aided by continued structural studies on proteins of this interesting enzyme family.

Natalie De Souza


  1. A. Tchigvintsev et al. Biochemical and structural studies of uncharacterized protein PA0743 from Pseudomonas aeruginosa revealed NAD+-dependent L-Serine dehydrogenase.
    J Biol Chem 287, 1874-1883 (2012). doi:10.1074/jbc.M111.294561

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health