FHMCD_RHILO
ID FHMCD_RHILO Reviewed; 309 AA.
AC Q988C8; B6ZH65;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=5-formyl-3-hydroxy-2-methylpyridine 4-carboxylate 5-dehydrogenase {ECO:0000303|PubMed:19218190};
DE Short=FHMPC dehydrogenase {ECO:0000303|PubMed:19218190};
DE EC=1.2.1.100 {ECO:0000269|PubMed:19218190};
GN Name=fhmpcd1 {ECO:0000312|EMBL:BAH02784.1};
GN OrderedLocusNames=mlr6793 {ECO:0000312|EMBL:BAB53022.1};
OS Mesorhizobium japonicum (strain LMG 29417 / CECT 9101 / MAFF 303099)
OS (Mesorhizobium loti (strain MAFF 303099)).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Phyllobacteriaceae; Mesorhizobium.
OX NCBI_TaxID=266835;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-15, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-137 AND GLU-149.
RC STRAIN=LMG 29417 / CECT 9101 / MAFF 303099;
RX PubMed=19218190; DOI=10.1093/jb/mvp007;
RA Yokochi N., Yoshikane Y., Matsumoto S., Fujisawa M., Ohnishi K., Yagi T.;
RT "Gene identification and characterization of 5-formyl-3-hydroxy-2-
RT methylpyridine 4-carboxylic acid 5-dehydrogenase, an NAD+-dependent
RT dismutase.";
RL J. Biochem. 145:493-503(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LMG 29417 / CECT 9101 / MAFF 303099;
RX PubMed=11214968; DOI=10.1093/dnares/7.6.331;
RA Kaneko T., Nakamura Y., Sato S., Asamizu E., Kato T., Sasamoto S.,
RA Watanabe A., Idesawa K., Ishikawa A., Kawashima K., Kimura T., Kishida Y.,
RA Kiyokawa C., Kohara M., Matsumoto M., Matsuno A., Mochizuki Y.,
RA Nakayama S., Nakazaki N., Shimpo S., Sugimoto M., Takeuchi C., Yamada M.,
RA Tabata S.;
RT "Complete genome structure of the nitrogen-fixing symbiotic bacterium
RT Mesorhizobium loti.";
RL DNA Res. 7:331-338(2000).
RN [3] {ECO:0007744|PDB:4OM8}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH NAD, AND SUBUNIT.
RC STRAIN=LMG 29417 / CECT 9101 / MAFF 303099;
RX PubMed=25446130; DOI=10.1016/j.bbrc.2014.11.028;
RA Mugo A.N., Kobayashi J., Mikami B., Yoshikane Y., Yagi T., Ohnishi K.;
RT "Crystal structure of 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid
RT 5-dehydrogenase, an NAD-dependent dismutase from Mesorhizobium loti.";
RL Biochem. Biophys. Res. Commun. 456:35-40(2015).
CC -!- FUNCTION: Involved in the degradation of pyridoxine (vitamin B(6)).
CC Catalyzes the oxidation of 5-formyl-3-hydroxy-2-methylpyridine-4-
CC carboxylate (FHMPC) by NAD(+) to 5-hydroxy-6-methylpyridine-3,4-
CC dicarboxylate (HMPDC) (PubMed:19218190). Can also catalyze the
CC reduction of FHMPC by NADH to 4-pyridoxic acid (PubMed:19218190).
CC {ECO:0000269|PubMed:19218190}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-formyl-3-hydroxy-2-methylpyridine-4-carboxylate + H2O +
CC NAD(+) = 5-hydroxy-6-methylpyridine-3,4-dicarboxylate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:19693, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:77620,
CC ChEBI:CHEBI:140633; EC=1.2.1.100;
CC Evidence={ECO:0000269|PubMed:19218190};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19694;
CC Evidence={ECO:0000269|PubMed:19218190};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-formyl-3-hydroxy-2-methylpyridine-4-carboxylate + H(+) +
CC NADH = 4-pyridoxate + NAD(+); Xref=Rhea:RHEA:63260,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30959, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:140633;
CC Evidence={ECO:0000269|PubMed:19218190};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63261;
CC Evidence={ECO:0000269|PubMed:19218190};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=48.2 uM for FHMPC (at pH 8.0, in the presence of NAD(+))
CC {ECO:0000269|PubMed:19218190};
CC KM=24.9 uM for FHMPC (at pH 8.0, in the presence of NADH)
CC {ECO:0000269|PubMed:19218190};
CC KM=34.3 uM for NAD(+) (at pH 8.0) {ECO:0000269|PubMed:19218190};
CC KM=12.4 uM for NADH (at pH 8.0) {ECO:0000269|PubMed:19218190};
CC Note=kcat is 204 sec(-1) for the oxidation of FHMPC. kcat is 217
CC sec(-1) for the reduction of FHMPC. {ECO:0000269|PubMed:19218190};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:19218190};
CC Temperature dependence:
CC Optimum temperature is 55 degrees Celsius.
CC {ECO:0000269|PubMed:19218190};
CC -!- PATHWAY: Cofactor degradation; B6 vitamer degradation.
CC {ECO:0000269|PubMed:19218190}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19218190,
CC ECO:0000269|PubMed:25446130}.
CC -!- DISRUPTION PHENOTYPE: Disruption mutant cannot grow on a synthetic
CC medium containing pyridoxine, 4-pyridoxic acid or FHMPC as a sole
CC carbon and nitrogen source. {ECO:0000269|PubMed:19218190}.
CC -!- SIMILARITY: Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AB362565; BAH02784.1; -; Genomic_DNA.
DR EMBL; BA000012; BAB53022.1; -; Genomic_DNA.
DR RefSeq; WP_010914332.1; NC_002678.2.
DR PDB; 4OM8; X-ray; 1.55 A; A/B=1-309.
DR PDBsum; 4OM8; -.
DR AlphaFoldDB; Q988C8; -.
DR SMR; Q988C8; -.
DR STRING; 266835.14026425; -.
DR EnsemblBacteria; BAB53022; BAB53022; BAB53022.
DR KEGG; mlo:mlr6793; -.
DR PATRIC; fig|266835.9.peg.5406; -.
DR eggNOG; COG1250; Bacteria.
DR HOGENOM; CLU_009834_2_0_5; -.
DR OMA; CNGHYYM; -.
DR OrthoDB; 862072at2; -.
DR BioCyc; MetaCyc:MON-20508; -.
DR BRENDA; 1.1.99.42; 15627.
DR BRENDA; 1.2.1.100; 15627.
DR UniPathway; UPA00192; -.
DR Proteomes; UP000000552; Chromosome.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:InterPro.
DR GO; GO:0042820; P:vitamin B6 catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR002204; 3-OH-isobutyrate_DH-rel_CS.
DR InterPro; IPR022694; 3-OHacyl-CoA_DH.
DR InterPro; IPR006180; 3-OHacyl-CoA_DH_CS.
DR InterPro; IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
DR InterPro; IPR006108; 3HC_DH_C.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 1.
DR Pfam; PF02737; 3HCDH_N; 1.
DR PIRSF; PIRSF000105; HCDH; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00895; 3_HYDROXYISOBUT_DH; 1.
DR PROSITE; PS00067; 3HCDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; NAD; Nucleotide-binding;
KW Oxidoreductase.
FT CHAIN 1..309
FT /note="5-formyl-3-hydroxy-2-methylpyridine 4-carboxylate 5-
FT dehydrogenase"
FT /id="PRO_0000450075"
FT BINDING 12..13
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25446130"
FT BINDING 32
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25446130"
FT BINDING 87..89
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25446130"
FT BINDING 94
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:25446130"
FT SITE 137
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000305|PubMed:25446130"
FT MUTAGEN 137
FT /note="H->L: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19218190"
FT MUTAGEN 149
FT /note="E->Q: Shows a different pH optimum depending on the
FT cosubstrate."
FT /evidence="ECO:0000269|PubMed:19218190"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 14..23
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 35..54
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 73..77
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 91..102
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:4OM8"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 158..170
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:4OM8"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 187..203
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 209..219
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 229..236
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 238..251
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 260..267
FT /evidence="ECO:0007829|PDB:4OM8"
FT TURN 273..276
FT /evidence="ECO:0007829|PDB:4OM8"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:4OM8"
FT HELIX 284..305
FT /evidence="ECO:0007829|PDB:4OM8"
SQ SEQUENCE 309 AA; 33061 MW; 63283FA5C583AF7C CRC64;
MIRNIAIIGL GTMGPGMAAR LARGGLQVVA YDVAPAAIER ARSMLSVAET VLDALGIALP
SAGVGTVRFT DDIGDAVSGA DLVIENVPEN ISIKADVYRT IDGLIGQDTI VASDTSGIPI
TKLQAHISYP ERMVGMHWSN PPHIIPMIEV IAGEKTAPQT VATIRDLIRS IGLLPVVVKK
DVPGFVENRV LYALLREAVD LVERGVIDPE DLDTCVSWGI GYKIAVIGPM ALLDMAGLDI
YKSVSSFLNA DLSNRDDVAP MVLEKTSASK FGIKSGEGMF CYTPEQTKAL QAERARKLVA
VRRILEGRE
