Flavin_ReductFlavin reductase like domain
|SMART accession number:||SM00903|
|Description:||This entry represents the FMN-binding domain found in NAD(P)H-flavin oxidoreductases (flavin reductases), a class of enzymes capable of producing reduced flavin for bacterial bioluminescence and other biological processes. This domain is also found in various other oxidoreductase and monooxygenase enzymes (PUBMED:12829278), (PUBMED:15461461), (PUBMED:11017201). This domain consists of a beta-barrel with Greek key topology, and is related to the ferredoxin reductase-like FAD-binding domain. The flavin reductases have a different dimerisation mode than that found in the PNP oxidase-like family, which also carries an FMN-binding domain with a similar topology.|
|Interpro abstract (IPR002563):|
This domain can be found in NAD(P)H-flavin oxidoreductases (flavin reductases), a class of enzymes capable of producing reduced flavin for bacterial bioluminescence and other biological processes, and various other oxidoreductase and monooxygenase enzymes [(PUBMED:12829278), (PUBMED:15461461), (PUBMED:11017201)].
This domain consists of a beta-barrel with Greek key topology, and is related to the ferredoxin reductase-like FAD-binding domain. The flavin reductases have a different dimerisation mode than that found in the PNP oxidase-like family, which also carries an FMN-binding domain with a similar topology.
|GO function:||FMN binding (GO:0010181)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing Flavin_Reduct domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Flavin_Reduct domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing Flavin_Reduct domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
Cellular role: metabolism
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Russell TR, Tu SC
- Aminobacter aminovorans NADH:flavin oxidoreductase His140: a highlyconserved residue critical for NADH binding and utilization.
- Biochemistry. 2004; 43: 12887-93
- Display abstract
Homodimeric FRD(Aa) Class I is an NADH:flavin oxidoreductase fromAminobacter aminovorans. It is unusual because it contains an FMN cofactorbut utilizes a sequential-ordered kinetic mechanism. Because little isknown about NADH-specific flavin reductases in general and FRD(Aa) inparticular, this study aimed to further explore FRD(Aa) by identifying thefunctionalities of a key residue. A sequence alignment of FRD(Aa) withseveral known and hypothetical flavoproteins in the same subfamily revealswithin the flavin reductase active-site domain a conserved GDH motif,which is believed to be responsible for the enzyme and NADH interaction.Mutation of the His140 in this GDH motif to alanine reduced FRD(Aa)activity to <3%. An ultrafiltration assay and fluorescence quenchingdemonstrated that H140A FRD(Aa) binds FMN in the same 1:1 stoichiometricratio as the wild-type enzyme, but with slightly weakened affinity (K(d) =0.9 microM). Anaerobic stopped-flow studies were carried out using boththe native and mutated FRD(Aa). Similar to the native enzyme, H140AFRD(Aa) was also able to reduce the FMN cofactor by NADH although muchless efficiently. Kinetic analysis of anaerobic reduction measurementsindicated that the His140 residue of FRD(Aa) was essential to NADHbinding, as well as important for the reduction of the FMN cofactor. Forthe native enzyme, the cofactor reduction was followed by at least oneslower step in the catalytic pathway.
- Schroder I, Johnson E, de Vries S
- Microbial ferric iron reductases.
- FEMS Microbiol Rev. 2003; 27: 427-47
- Display abstract
Almost all organisms require iron for enzymes involved in essentialcellular reactions. Aerobic microbes living at neutral or alkaline pHencounter poor iron availability due to the insolubility of ferric iron.Assimilatory ferric reductases are essential components of the ironassimilatory pathway that generate the more soluble ferrous iron, which isthen incorporated into cellular proteins. Dissimilatory ferric reductasesare essential terminal reductases of the iron respiratory pathway iniron-reducing bacteria. While our understanding of dissimilatory ferricreductases is still limited, it is clear that these enzymes are distinctfrom the assimilatory-type ferric reductases. Research over the last 10years has revealed that most bacterial assimilatory ferric reductases areflavin reductases, which can serve several physiological roles. Thisarticle reviews the physiological function and structure of assimilatoryand dissimilatory ferric reductases present in the Bacteria, Archaea andYeast. Ferric reductases do not form a single family, but appear to bedistinct enzymes suggesting that several independent strategies for ironreduction may have evolved.
- Christendat D et al.
- Structural proteomics of an archaeon.
- Nat Struct Biol. 2000; 7: 903-9
- Display abstract
A set of 424 nonmembrane proteins from Methanobacteriumthermoautotrophicum were cloned, expressed and purified for structuralstudies. Of these, approximately 20% were found to be suitable candidatesfor X-ray crystallographic or NMR spectroscopic analysis without furtheroptimization of conditions, providing an estimate of the number of themost accessible structural targets in the proteome. A retrospectiveanalysis of the experimental behavior of these proteins suggested somesimple relations between sequence and solubility, implying that data basesof protein properties will be useful in optimizing high throughputstrategies. Of the first 10 structures determined, several provided cluesto biochemical functions that were not detectable from sequence analysis,and in many cases these putative functions could be readily confirmed bybiochemical methods. This demonstrates that structural proteomics isfeasible and can play a central role in functional genomics.
- Parry RJ, Li W
- An NADPH:FAD oxidoreductase from the valanimycin producer, Streptomycesviridifaciens. Cloning, analysis, and overexpression.
- J Biol Chem. 1997; 272: 23303-11
- Display abstract
The valanimycin producer Streptomyces viridifaciens contains atwo-component enzyme system that catalyzes the oxidation of isobutylamineto isobutylhydroxylamine. One component of this enzyme system isisobutylamine hydroxylase, and the other component is a flavin reductase.The gene (vlmR) encoding the flavin reductase required by isobutylaminehydroxylase has been cloned from S. viridifaciens by chromosome walking.The gene codes for a protein of 194 amino acids with a calculated mass of21,265 Da and a calculated pI of 10.2. Overexpression of the vlmR gene inEscherichia coli as an N-terminal His-tag derivative yielded a solubleprotein that was purified to homogeneity. Removal of the N-terminalHis-tag from the overexpressed protein by thrombin cleavage also produceda soluble protein. Both forms of the protein exhibited a high degree offlavin reductase activity, and the thrombin-cleaved form functioned incombination with isobutylamine hydroxylase to catalyze the conversion ofisobutylamine to isobutylhydroxylamine. Kinetic data indicate that theoverexpressed protein utilizes FAD and NADPH in preference to FMN,riboflavin, and NADH. The deduced amino acid sequence of the VlmR proteinexhibited similarity to several other flavin reductases that mayconstitute a new family of flavin reductases.
- Blanc V, Lagneaux D, Didier P, Gil P, Lacroix P, Crouzet J
- Cloning and analysis of structural genes from Streptomycespristinaespiralis encoding enzymes involved in the conversion ofpristinamycin IIB to pristinamycin IIA (PIIA): PIIA synthase andNADH:riboflavin 5'-phosphate oxidoreductase.
- J Bacteriol. 1995; 177: 5206-14
- Display abstract
In Streptomyces pristinaespiralis, two enzymes are necessary forconversion of pristinamycin IIB (PIIB) to pristinamycin IIA (PIIA), themajor component of pristinamycin (D. Thibaut, N. Ratet, D. Bisch, D.Faucher, L. Debussche, and F. Blanche, J. Bacteriol. 177:5199-5205, 1995);these enzymes are PIIA synthase, a heterodimer composed of the SnaA andSnaB proteins, which catalyzes the oxidation of PIIB to PIIA, and theNADH:riboflavin 5'-phosphate oxidoreductase (hereafter called FMNreductase), the SnaC protein, which provides the reduced form of flavinmononucleotide for the reaction. By using oligonucleotide probes designedfrom limited peptide sequence information of the purified proteins, thecorresponding genes were cloned from a genomic library of S.pristinaespiralis. SnaA and SnaB showed no significant similarity withproteins from databases, but SnaA and SnaB had similar protein domains.Disruption of the snaA gene in S. pristinaespiralis led to accumulation ofPIIB. Complementation of a S. pristinaespiralis PIIA-PIIB+ mutant with thesnaA and snaB genes, cloned in a low-copy-number plasmid, partiallyrestored production of PIIA. The deduced amino acid sequence of the snaCgene showed no similarity to the sequences of other FMN reductases but was39% identical with the product of the actVB gene of the actinorhodincluster of Streptomyces coelicolor A(3)2, likely to be involved in thedimerization step of actinorhodin biosynthesis. Furthermore, an S.coelicolor A(3)2 mutant blocked in this step was successfully complementedby the snaC gene, restoring the production of actinorhodin.
- Structure (3D structures containing this domain)
3D Structures of Flavin_Reduct domains in PDB
PDB code Main view Title 1eje CRYSTAL STRUCTURE OF AN FMN-BINDING PROTEIN 1i0r CRYSTAL STRUCTURE OF FERRIC REDUCTASE FROM ARCHAEOGLOBUS FULGIDUS 1i0s ARCHAEOGLOBUS FULGIDUS FERRIC REDUCTASE COMPLEX WITH NADP+ 1rz0 Flavin reductase PheA2 in native state 1rz1 Reduced flavin reductase PheA2 in complex with NAD 1usc PUTATIVE STYRENE MONOOXYGENASE SMALL COMPONENT 1usf PUTATIVE STYRENE MONOOXYGENASE SMALL COMPONENT WITH BOUND NADP+ 1wgb Crystal structure of a probable flavoprotein from Thermus thermophilus HB8 1yoa Crystal structure of a probable flavoprotein from Thermus thermophilus HB8 2d36 The Crystal Structure of Flavin Reductase HpaC 2d37 The Crystal Structure of Flavin Reductase HpaC complexed with NAD+ 2d38 The Crystal Structure of Flavin Reductase HpaC complexed with NADP+ 2d5m Flavoredoxin of Desulfovibrio vulgaris (Miyazaki F) 2ecr Crystal structure of the ligand-free form of the flavin reductase component (HpaC) of 4-hydroxyphenylacetate 3-monooxygenase 2ecu Crystal structure of flavin reductase component (HpaC) of 4-hydroxyphenylacetate 3-monooxygenase 2ed4 Crystal structure of flavin reductase HpaC complexed with FAD and NAD 2qck Crystal structure of flavin reductase domain protein (YP_831077.1) from Arthrobacter sp. FB24 at 1.90 A resolution 2r0x Crystal structure of a putative flavin reductase (ycdh, hs_1225) from haemophilus somnus 129pt at 1.06 A resolution 2r6v Crystal structure of FMN-binding protein (NP_142786.1) from Pyrococcus horikoshii at 1.35 A resolution 3bnk X-ray crystal structure of Flavoredoxin from Methanosarcina acetivorans 3bpk Crystal structure of nitrilotriacetate monooxygenase component B from Bacillus cereus 3cb0 CobR 3e4v Crystal structure of NADH:FMN oxidoreductase like protein in complex with FMN (YP_544701.1) from METHYLOBACILLUS FLAGELLATUS KT at 1.40 A resolution 3hmz CRYSTAL STRUCTURE OF A FMN-BINDING DOMAIN OF FLAVIN REDUCTASES-LIKE ENZYME (SBAL_0626) FROM SHEWANELLA BALTICA OS155 AT 1.50 A RESOLUTION 3k86 Crystal structure of NADH:FAD oxidoreductase (TftC) - apo form 3k87 Crystal structure of NADH:FAD oxidoreductase (TftC) - FAD complex 3k88 Crystal structure of NADH:FAD oxidoreductase (TftC) - FAD, NADH complex 3nfw Crystal structure of nitrilotriacetate monooxygenase component B (A0R521 homolog) from Mycobacterium thermoresistibile 3pft Crystal Structure of Untagged C54A Mutant Flavin Reductase (DszD) in Complex with FMN From Mycobacterium goodii 3rh7 Crystal structure of a hypothetical oxidoreductase (SMA0793) from sinorhizobium meliloti 1021 at 3.00 A resolution 3zoc Crystal structure of FMN-binding protein (NP_142786.1) from Pyrococcus horikoshii with bound p-hydroxybenzaldehyde 3zod Crystal structure of FMN-binding protein (NP_142786.1) from Pyrococcus horikoshii with bound benzene-1,4-diol 3zoe Crystal structure of FMN-binding protein (YP_005476) from Thermus thermophilus with bound p-hydroxybenzaldehyde 3zof Crystal structure of FMN-binding protein (YP_005476) from Thermus thermophilus with bound benzene-1,4-diol 3zog Crystal structure of FMN-binding protein (NP_142786.1) from Pyrococcus horikoshii with bound 1-Cyclohex-2-enone 3zoh Crystal structure of FMN-binding protein (YP_005476) from Thermus thermophilus with bound 1-Cyclohex-2-enone 4f07 Structure of the Styrene Monooxygenase Flavin Reductase (SMOB) from Pseudomonas putida S12 4hx6 The crystal structure of an oxidoreductase (SgcE6)from Streptomyces globisporus 4ira CobR in complex with FAD 4l82 Structure of a putative oxidoreductase from Rickettsia felis
- Links (links to other resources describing this domain)
PFAM Flavin_Reduct INTERPRO IPR002563