MF7000335 FHMPCDH 4om8 X-ray 1.55 Homodimer Mesorhizobium japonicum 25446130 Mugo AN, Kobayashi J, Mikami B, Yoshikane Y, Yagi T, Ohnishi K Biochem. Biophys. Res. Commun. 2015 1 456 35-40 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. GO:0050104 L-gulonate 3-dehydrogenase activity GO:0070403 NAD+ binding GO:0006631 fatty acid metabolic process GO:0042820 vitamin B6 catabolic process 2 1 Homooligomeric enzymes Homodimeric enzymes All chains according to the most probable oligomerization state stored in PDBe were considered. A 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylate 5-dehydrogenase Mesorhizobium japonicum Q988C8 1 309 100% MIRNIAIIGLGTMGPGMAARLARGGLQVVAYDVAPAAIERARSMLSVAETVLDALGIALPSAGVGTVRFTDDIGDAVSGADLVIENVPENISIKADVYRTIDGLIGQDTIVASDTSGIPITKLQAHISYPERMVGMHWSNPPHIIPMIEVIAGEKTAPQTVATIRDLIRSIGLLPVVVKKDVPGFVENRVLYALLREAVDLVERGVIDPEDLDTCVSWGIGYKIAVIGPMALLDMAGLDIYKSVSSFLNADLSNRDDVAPMVLEKTSASKFGIKSGEGMFCYTPEQTKALQAERARKLVAVRRILEGRE 309 secondary structure helix 13 24 secondary structure helix 34 55 secondary structure helix 72 78 secondary structure helix 90 103 secondary structure helix 119 124 secondary structure helix 125 127 secondary structure helix 129 131 secondary structure helix 157 171 secondary structure helix 186 204 secondary structure helix 208 220 secondary structure helix 220 227 secondary structure helix 228 237 secondary structure helix 237 252 secondary structure helix 259 268 secondary structure helix 283 306 secondary structure strand 4 8 secondary structure strand 27 31 secondary structure strand 66 70 secondary structure strand 82 85 secondary structure strand 110 113 secondary structure strand 133 137 secondary structure strand 147 151 secondary structure strand 174 178 pfam PF02737 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain 4 181 A-2 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylate 5-dehydrogenase Mesorhizobium japonicum Q988C8 1 309 100% MIRNIAIIGLGTMGPGMAARLARGGLQVVAYDVAPAAIERARSMLSVAETVLDALGIALPSAGVGTVRFTDDIGDAVSGADLVIENVPENISIKADVYRTIDGLIGQDTIVASDTSGIPITKLQAHISYPERMVGMHWSNPPHIIPMIEVIAGEKTAPQTVATIRDLIRSIGLLPVVVKKDVPGFVENRVLYALLREAVDLVERGVIDPEDLDTCVSWGIGYKIAVIGPMALLDMAGLDIYKSVSSFLNADLSNRDDVAPMVLEKTSASKFGIKSGEGMFCYTPEQTKALQAERARKLVAVRRILEGRE 309 pfam PF02737 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain 4 181 Indirect evidence Only some parts of the structure participates in mutual synergistic folding. - It is a dimer. Dissociation cannot be detected by differential scanning calorimetry (PMID:35041856). The helical dimerization domain is very tightly packed. A N/A A-2 N/A