Crystal structure of 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase, an NAD⁺-dependent dismutase from Mesorhizobium loti

Biochem Biophys Res Commun. 2015 Jan 2;456(1):35-40. doi: 10.1016/j.bbrc.2014.11.028. Epub 2014 Nov 18.


5-Formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase (FHMPCDH) from Mesorhizobium loti is the fifth enzyme in degradation pathway I for pyridoxine. The enzyme catalyzes a dismutation reaction: the oxidation of 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid (FHMPC) to 3-hydroxy-2-methylpyridine 4,5-dicarboxylic acid with NAD(+) and reduction of FHMPC to 4-pyridoxic acid with NADH. FHMPCDH belongs to the l-3-hydroxyacyl-CoA dehydrogenase (HAD) family. The crystal structure was determined by molecular replacement and refined to a resolution of 1.55Å (R-factor of 16.4%, Rfree=19.4%). There were two monomers in the asymmetric unit. The overall structure of the monomer consisted of N- and C-terminal domains connected by a short linker loop. The monomer was similar to members of the HAD family (RMSD=1.9Å). The active site was located between the domains and highly conserved to that of human heart l-3-hydroxyacyl-CoA dehydrogenase (HhHAD). His-Glu catalytic dyad, a serine and two asparagine residues of HhHAD were conserved. Ser116, His137 and Glu149 in FHMPCDH are connected by a hydrogen bonding network forming a catalytic triad. The functions of the active site residues in the reaction mechanism are discussed.

Keywords: 3-Hydroxyacyl-CoA dehydrogenase; 5-Formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase; Dismutase; Mesorhizobium loti; Nicotinamide adenine dinucleotide; Vitamin B(6)-degradation pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl-CoA Dehydrogenase / chemistry
  • Alcohol Oxidoreductases / chemistry*
  • Bacterial Proteins / chemistry*
  • Catalysis
  • Catalytic Domain
  • Conserved Sequence
  • Crystallography, X-Ray
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hydrogen Bonding
  • Mesorhizobium / enzymology*
  • Models, Molecular
  • Myocardium / enzymology
  • NAD / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Vitamin B 6 / chemistry


  • Bacterial Proteins
  • NAD
  • Vitamin B 6
  • Alcohol Oxidoreductases
  • 5-formyl-3-hydroxy-2-methylpyridine-4-carboxylic acid dehydrogenase
  • 3-Hydroxyacyl-CoA Dehydrogenase