Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Structural, Biochemical, and Evolutionary Characterizations of Glyoxylate/Hydroxypyruvate Reductases Show Their Division into Two Distinct Subfamilies

Journal Article · · Biochemistry
 [1];  [2];  [1];  [2];  [2];  [2];  [3];  [3];  [3];  [1]
  1. Univ. of Virginia, Charlottesville, VA (United States); Univ. of Warsaw (Poland)
  2. Univ. of Virginia, Charlottesville, VA (United States)
  3. Univ. of Warsaw (Poland)
+ Show Author Affiliations
The d-2-hydroxyacid dehydrogenase (2HADH) family illustrates a complex evolutionary history with multiple lateral gene transfers and gene duplications and losses. As a result, the exact functional annotation of individual members can be extrapolated to a very limited extent. Here, we revise the previous simplified view on the classification of the 2HADH family; specifically, we show that the previously delineated glyoxylate/hydroxypyruvate reductase (GHPR) subfamily consists of two evolutionary separated GHRA and GHRB subfamilies. We compare two representatives of these subfamilies from Sinorhizobium meliloti (SmGhrA and SmGhrB), employing a combination of biochemical, structural, and bioinformatics approaches. Our kinetic results show that both enzymes reduce several 2-ketocarboxylic acids with overlapping, but not equivalent, substrate preferences. SmGhrA and SmGhrB show highest activity with glyoxylate and hydroxypyruvate, respectively; in addition, only SmGhrB reduces 2-keto-d-gluconate, and only SmGhrA reduces pyruvate (with low efficiency). We present nine crystal structures of both enzymes in apo forms and in complexes with cofactors and substrates/substrate analogues. In particular, we determined a crystal structure of SmGhrB with 2-keto-d-gluconate, which is the biggest substrate cocrystallized with a 2HADH member. Here, the structures reveal significant differences between SmGhrA and SmGhrB, both in the overall structure and within the substrate-binding pocket, offering insight into the molecular basis for the observed substrate preferences and subfamily differences. In addition, we provide an overview of all GHRA and GHRB structures complexed with a ligand in the active site.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; NIGMS; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1424792
Journal Information:
Biochemistry, Journal Name: Biochemistry Journal Issue: 6 Vol. 57; ISSN 0006-2960
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

References (55)

Molstack-Interactive visualization tool for presentation, interpretation, and validation of macromolecules and electron density maps: Molstack journal September 2017
A thioredoxin fusion protein of VanH, a D-lactate dehydrogenase from Enterococcus faecium : Cloning, expression, purification, kinetic analysis, and crystallization journal May 1998
Characterization of enzymes involved in the central metabolism of Gluconobacter oxydans journal July 2010
A new family of 2-hydroxyacid dehydrogenases journal December 1989
Kinetics of Escherichia coli B D-Lactate Dehydrogenase and Evidence for Pyruvate-controlled Change in Conformation journal May 1968
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Large-scale applications of NAD(P)-dependent oxidoreductases: recent developments journal December 1999
A new d-2-hydroxyacid dehydrogenase with dual coenzyme-specificity from Haloferax mediterranei, sequence analysis and heterologous overexpression journal November 2006
A preliminary account of the properties of recombinant human Glyoxylate reductase (GRHPR), LDHA and LDHB with glyoxylate, and their potential roles in its metabolism journal December 2005
Identification of a novel glyoxylate reductase supports phylogeny-based enzymatic substrate specificity prediction journal September 2007
Novel fungal phenylpyruvate reductase belongs to d-isomer-specific 2-hydroxyacid dehydrogenase family journal December 2011
Characterization and crystal structure of a first fungal glyoxylate reductase from Paecilomyes thermophila journal June 2014
Structural Basis of Substrate Specificity in Human Glyoxylate Reductase/Hydroxypyruvate Reductase journal June 2006
Inference of Macromolecular Assemblies from Crystalline State journal September 2007
A New Generation of Crystallographic Validation Tools for the Protein Data Bank journal October 2011
A General Tool for Engineering the NAD/NADP Cofactor Preference of Oxidoreductases journal October 2016
Crystal Structures of Phosphite Dehydrogenase Provide Insights into Nicotinamide Cofactor Regeneration journal May 2012
Purification, Cloning and Functional Expression of hydroxyphenylpyruvate Reductase Involved in Rosmarinic Acid Biosynthesis in Cell Cultures of Coleus Blumei journal February 2004
How rhizobial symbionts invade plants: the Sinorhizobium–Medicago model journal August 2007
New insights into the mechanism of substrates trafficking in Glyoxylate/Hydroxypyruvate reductases journal February 2016
Biochemical characterization of the 2-ketoacid reductases encoded by ycdW and yiaE genes in Escherichia coli journal March 2001
Purification and characterization of a novel NADPH(NADH)-dependent hydroxypyruvate reductase from spinach leaves. Comparison of immunological properties of leaf hydroxypyruvate reductases journal February 1988
Mechanistic and active-site studies on d(–)-mandelate dehydrogenase from Rhodotorula graminis journal January 1992
NAD+-dependent formate dehydrogenase journal August 1994
Purification and Characterization of a Novel Phosphorus-oxidizing Enzyme from Pseudomonas stutzeri WM88 journal February 2001
Hydrolase Regulates NAD+ Metabolites and Modulates Cellular Redox journal April 2009
trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses journal June 2009
The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II journal October 1999
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability journal January 2013
UniProt: a hub for protein information journal October 2014
Horizontal gene transfer in the acquisition of novel traits by metazoans journal February 2014
A Cytosolic Pathway for the Conversion of Hydroxypyruvate to Glycerate during Photorespiration in Arabidopsis journal October 2008
Coot model-building tools for molecular graphics journal November 2004
Optimal description of a protein structure in terms of multiple groups undergoing TLS motion journal March 2006
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes journal July 2006
The Buccaneer software for automated model building. 1. Tracing protein chains journal August 2006
Structure of archaeal glyoxylate reductase from Pyrococcus horikoshii OT3 complexed with nicotinamide adenine dinucleotide phosphate journal February 2007
Structures of the apo and holo forms of formate dehydrogenase from the bacterium Moraxella sp. C-1: towards understanding the mechanism of the closure of the interdomain cleft journal November 2009
MolProbity : all-atom structure validation for macromolecular crystallography journal December 2009
Molecular replacement with MOLREP journal December 2009
Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plant Coleus blumei Benth. journal April 2010
Overview of the CCP 4 suite and current developments journal March 2011
Refinement of Macromolecular Structures by the Maximum-Likelihood Method journal May 1997
Data to knowledge: how to get meaning from your result journal January 2015
Fitmunk : improving protein structures by accurate, automatic modeling of side-chain conformations journal January 2016
A public database of macromolecular diffraction experiments journal October 2016
The Composite Genome of the Legume Symbiont Sinorhizobium meliloti journal July 2001
phyloXML: XML for evolutionary biology and comparative genomics journal October 2009
RegPrecise 3.0 – A resource for genome-scale exploration of transcriptional regulation in bacteria journal January 2013
Enantioselective cascade biocatalysis for deracemization of 2-hydroxy acids using a three-enzyme system journal September 2016
FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments journal March 2010
Chemical Rescue and Inhibition Studies to Determine the Role of Arg301 in Phosphite Dehydrogenase journal January 2014
Comparative genomics and evolution of regulons of the LacI-family transcription factors journal June 2014
Biocatalytic Synthesis of Chiral Alcohols and Amino Acids for Development of Pharmaceuticals journal October 2013
Enantioselective cascade biocatalysis for deracemization of 2-hydroxy acids using a three-enzyme system collection January 2016

Cited By (6)

Classification, substrate specificity and structural features of D-2-hydroxyacid dehydrogenases: 2HADH knowledgebase journal December 2018
Molstack: A platform for interactive presentations of electron density and cryo‐EM maps and their interpretations journal October 2019
The Integrated Resource for Reproducibility in Macromolecular Crystallography: Experiences of the first four years journal November 2019
Refining the macromolecular model – achieving the best agreement with the data from X-ray diffraction experiment journal September 2018
Structural and biochemical analysis of Bacillus anthracis prephenate dehydrogenase reveals an unusual mode of inhibition by tyrosine via the ACT domain journal December 2019
A Genetic Screen To Identify Genes Influencing the Secondary Redox Couple NADPH/NADP + in the Yeast Saccharomyces cerevisiae journal November 2019

Similar Records

Purification and properties of hydroxypyruvate: L-alanine transaminase from rabbit liver
Journal Article · Fri Nov 30 23:00:00 EST 1973 · Arch. Biochem. Biophys.; (United States) · OSTI ID:7230450
Extent and Origins of Functional Diversity in a Subfamily of Glycoside Hydrolases
Journal Article · Thu Mar 14 20:00:00 EDT 2019 · Journal of Molecular Biology · OSTI ID:1546759
Metabolism of hydroxypyruvate in a mutant of barley lacking NADH-dependent hydroxypyruvate reductase, an important photorespiratory enzyme activity
Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Plant Physiology; (USA) · OSTI ID:5914625

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
anions
chemical structure
crystal structure
ligands
peptides and proteins