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Information on EC 1.5.1.30 - flavin reductase (NADPH) and Organism(s) Homo sapiens and UniProt Accession P30043
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1.5.1.30 flavin reductase (NADPH)IUBMB Comments
The enzyme reduces riboflavin, and, less efficiently, FMN and FAD. NADH is oxidized less efficiently than NADPH.
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Word Map
- 1.5.1.30
- monooxygenase
- mononucleotide
- harveyi
-
flavin-dependent
- fmnh2
- dibenzothiophene
- fischeri
-
desulfurization
- halogenases
-
oxygen-insensitive
-
nadh:flavin
-
biodesulfurization
- nitroreductases
- leiognathi
-
fadh2-dependent
- 2-hydroxybiphenyl
-
fmn-dependent
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
flavin reductase, blvrb, nadph-dependent diaphorase, flavin oxidoreductase, biliverdin reductase b, nadph-flavin reductase, flavin reductase p, nadph:fmn oxidoreductase, nfra1, nadph-specific flavin reductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Biliverdin-IX beta-reductase
-
-
-
-
FLR
-
-
-
-
GHBP
-
-
-
-
Green heme binding protein
-
-
-
-
NADPH-dependent diaphorase
-
-
-
-
NADPH-flavin reductase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
reduced-riboflavin:NADP+ oxidoreductase
The enzyme reduces riboflavin, and, less efficiently, FMN and FAD. NADH is oxidized less efficiently than NADPH.
CAS REGISTRY NUMBER
COMMENTARY
56626-29-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
FAD + NADPH + H+
FADH2 + NADP+
-
specific activity for the reduction of oxidized riboflavin, FMN and FAD is similar
-
-
?
oxidized 2,6-dichlorophenolindophenol + NADPH + H+
reduced 2,6-dichlorophenolindophenol + NADP+
-
-
-
-
?
oxidized riboflavin + NADPH + H+
reduced riboflavin + NADP+
-
specific activity for the reduction of oxidized riboflavin, FMN and FAD is similar
-
-
?
FAD + NADPH + H+
FADH2 + NADP+
the enzyme (BLVRB) binds its coenzyme NADPH 500fold more tightly than its substrate FAD
-
-
?
FMN + NADPH + H+
FMNH2 + NADP+
-
specific activity for the reduction of oxidized riboflavin, FMN and FAD is similar
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
-
the FMN reductase activity is highly specific for NADPH, and the activity with NADH is 10% of that with NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
Fe2+, Fe3+, Mg2+, and Ca2+ do not affect the enzyme activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lumichrome
competitive inhibitor against FMN and a mixed inhibitor of NADPH
mesobiliverdin XIIIa
competitive kinetics with FMN and mixed inhibition kinetics with NADPH
NADP+
-
0.1 mM, about 50% inhibition at no inhibition by NAD+ at pH 7.5, 12% inhibition at pH 4.8
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
enzyme coexpression with gene dcs-1 is induced by heat shock
-
additional information
-
enzyme coexpression with gene dcs-1 is induced by heat shock
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
coenzyme clamps formed by arginine side chains at two co-evolving positions within the active site serve to slow coenzyme release (Positions 14 and 78). Coenzyme release is further slowed by the weaker binding substrate, resulting in relatively slow turnover numbers
-
additional information
additional information
-
coenzyme clamps formed by arginine side chains at two co-evolving positions within the active site serve to slow coenzyme release (Positions 14 and 78). Coenzyme release is further slowed by the weaker binding substrate, resulting in relatively slow turnover numbers
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 8
-
pH 4.5: about 85% of maximal activity, pH 8.0: about 45% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme biliverdin reductase/flavin reductase (NADPH)
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the enzyme is predominant during fetal development but sometimes detectable through adulthood
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
heme degradation enzyme biliverdin IXbeta reductase is required for stem cell glutamine metabolism
physiological function
the enzyme is a critical players in cellular redox regulation
evolution
a position 15 A away from the active site within human biliverdin reductase B (T164) is inherently dynamic and can be mutated to control global micro-millisecond motions and function. By comparing the inherent dynamics through nuclear magnetic resonance (NMR) relaxation approaches of evolutionarily distinct biliverdin reductase B homologues and by applying Relaxation And Single Site Multiple Mutations (RASSMM) approach that monitors both the functional and dynamic effects of multiple mutations to the single T164 site, it is discovered that the most dramatic mutagenic effects coincide with evolutionary changes and these modulate coenzyme binding
evolution
most BLVRB enzymes have an arginine at either residue 14 or residue 78 (human numbering), although a subset maintain an arginine at both sites. In primates, the two substitutions are made on the same branch separating the common ancestor of the Simiiformes (apes, new and old-world monkeys) with the common ancestor of the Haplorhini (i.e., after the split from the common ancestor with the tarsier). This suggests possible adaptive coevolution at these two sites and adjusting the location of this arginine may serve to fine-tune coenzyme binding in BLVRB enzymes
evolution
the study elucidates the role of the evolutionarily changing biliverdin reductase (BBLVRB) active site that serves to modulate coenzyme release and shows that coenzyme release is coupled to substrate turnover
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). BLVRB_HUMAN
206
0
22119
Swiss-Prot
other Location (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q14R
mutation at active site arginine residue increases coenzyme affinity
Q14R/R78G
double mutation within the enzyme exhibits a binding affinity that is close to the average between these two individual mutations
R78A
mutation leads to both an increase in active site micro-millisecond motions and an increase in the microscopic rate constants of coenzyme binding
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100
-
boiling of the enzyme leads to complete loss of the FMN reductase activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene fre-1, DNA and amino acid sequence determination and analysis, transcribed as a bicistronic pre-mRNA together with gene dcs-1, encoding Hint-related 7meGMP-directed hydrolase DCS-1
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yubisui, T.; Matsuki, T.; Takeshita, M.; Yoneyama, Y.
Characterization of the purified NADPH-flavin reductase of human erythrocytes
J. Biochem.
85
719-728
1979
Homo sapiens
Kwasnicka, D.A.; Krakowiak, A.; Thacker, C.; Brenner, C.; Vincent, S.R.
Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1
J. Biol. Chem.
278
39051-39058
2003
Caenorhabditis elegans, Homo sapiens (Q9UHB4), Homo sapiens
Chikuba, K.; Yubisui, T.; Shirabe, K.; Takeshita, M.
Cloning and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin reductase
Biochem. Biophys. Res. Commun.
198
1170-1176
1994
Homo sapiens (P30043), Homo sapiens
Yubisui, T.; Tamura, M.; Takeshita, M.
Characterization of a second form of NADPH-flavin reductase purified from human erythrocytes
Biochem. Int.
15
1-8
1987
Homo sapiens
Cunningham, O.; Gore, M.G.; Mantle, T.J.
Initial-rate kinetics of the flavin reductase reaction catalysed by human biliverdin-IXbeta reductase (BVR-B)
Biochem. J.
345
393-399
2000
Homo sapiens (P30043), Homo sapiens
Mancuso, C.
Biliverdin reductase as a target in drug research and development Facts and hypotheses
Free Radic. Biol. Med.
172
521-529
2021
Homo sapiens (P30043)
Li, Z.; Nesbitt, N.M.; Malone, L.E.; Gnatenko, D.V.; Wu, S.; Wang, D.; Zhu, W.; Girnun, G.D.; Bahou, W.F.
Heme degradation enzyme biliverdin IXbeta reductase is required for stem cell glutamine metabolism
Biochem. J.
475
1211-1223
2018
Homo sapiens (P30043)
Redzic, J.S.; Duff, M.R.; Blue, A.; Pitts, T.M.; Agarwal, P.; Eisenmesser, E.Z.
Modulating enzyme function via dynamic allostery within biliverdin reductase B
Front. Mol. Biosci.
8
691208
2021
Homo sapiens (P30043), Homo sapiens
Duff, M.R.; Redzic, J.S.; Ryan, L.P.; Paukovich, N.; Zhao, R.; Nix, J.C.; Pitts, T.M.; Agarwal, P.; Eisenmesser, E.Z.
Structure, dynamics and function of the evolutionarily changing biliverdin reductase B family
J. Biochem.
168
191-202
2020
Homo sapiens (P30043), Homo sapiens, Microcebus murinus (XP_020138941.1)
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