Summary: Riboflavin kinase

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Wikipedia: Riboflavin kinase
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Riboflavin kinase

riboflavin kinase

Crystal structure of riboflavin kinase from Thermoplasma acidophilum.^[1]

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles

Riboflavin kinase

crystal structure of flavin binding to fad synthetase from thermotoga maritina

Identifiers

Symbol

Flavokinase

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Riboflavin kinase

Identifiers

Symbol

Riboflavin_kinase

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

In enzymology, a riboflavin kinase (EC 2.7.1.26) is an enzyme that catalyzes the chemical reaction

ATP + riboflavin $\rightleftharpoons$ ADP + FMN

Thus, the two substrates of this enzyme are ATP and riboflavin, whereas its two products are ADP and FMN.

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (EC 2.7.1.26), which converts it into FMN, and FAD synthetase (EC 2.7.7.2), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme,^[2] the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family.^[3] The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases.^[4]

This enzyme belongs to the family of transferases, to be specific, those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:riboflavin 5'-phosphotransferase. This enzyme is also called flavokinase. This enzyme participates in riboflavin metabolism.

However, archaeal riboflavin kinases (EC 2.7.1.161) are, in general, utilizing CTP rather than ATP as the donor nucleotide, catalyzing the reaction

CTP + riboflavin $\rightleftharpoons$ CDP + FMN ^[5]

Riboflavin kinase can also be isolated from other types of bacteria, all with similar function but a different number of amino acids.

[edit] Structure

A hydropathy plot for Riboflavin Kinase.

The complete enzyme arrangement can be observed with X-ray crystallography and with NMR. The riboflavin kinase enzyme isolated from Thermoplasma acidophilum contains 220 amino acids. The structure of this enzyme has been determined X-ray crystallography at a resolution of 2.20 Å. Its secondary structure contains 69 residues (30%) in alpha helix form, and 60 residues (26%) a beta sheet conformation. The enzyme contains a magnesium binding site at amino acids 131 and 133, and a Flavin mononucleotide binding site at amino acids 188 and 195.

As of late 2007, 14 structures have been solved for this class of enzymes, with PDB accession codes 1N05, 1N06, 1N07, 1N08, 1NB0, 1NB9, 1P4M, 1Q9S, 2P3M, 2VBS, 2VBT, 3CTA, 2VBU, and 2VBV.

[edit] References

^ PDB 3CTA; Bonanno, J.B., Rutter, M., Bain, K.T., Mendoza, M., Romero, R., Smith, D., Wasserman, S., Sauder, J.M., Burley, S.K., Almo, S.C. (2008). Crystal structure of riboflavin kinase from Thermoplasma acidophilum.
^ Osterman AL, Zhang H, Zhou Q, Karthikeyan S (2003). "Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism". Biochemistry 42 (43): 12532–8. doi:10.1021/bi035450t. PMID 14580199.
^ Galluccio M, Brizio C, Torchetti EM, Ferranti P, Gianazza E, Indiveri C, Barile M (2007). "Over-expression in Escherichia coli, purification and characterization of isoform 2 of human FAD synthetase". Protein Expr. Purif. 52 (1): 175–81. doi:10.1016/j.pep.2006.09.002. PMID 17049878.
^ Srinivasan N, Krupa A, Sandhya K, Jonnalagadda S (2003). "A conserved domain in prokaryotic bifunctional FAD synthetases can potentially catalyze nucleotide transfer". Trends Biochem. Sci. 28 (1): 9–12. doi:10.1016/S0968-0004(02)00009-9. PMID 12517446.
^ Ammelburg M, Hartmann MD, Djuranovic S, Alva V, Koretke KK, Martin J, Sauer G, Truffault V, Zeth K, Lupas AN, Coles M (2007). "A CTP-Dependent Archaeal Riboflavin Kinase Forms a Bridge in the Evolution of Cradle-Loop Barrels". Structure. 12 (12): 1577–90. doi:10.1016/j.str.2007.09.027. PMID 18073108. http://www.uniprot.org/uniprot/Q9HJA6.

[edit] Further reading

CHASSY BM, ARSENIS C, MCCORMICK DB (1965). "THE EFFECT OF THE LENGTH OF THE SIDE CHAIN OF FLAVINS ON REACTIVITY WITH FLAVOKINASE". J. Biol. Chem. 240: 1338–40. PMID 14284745.
GIRI KV, KRISHNASWAMY PR, RAO NA (1958). "Studies on plant flavokinase". Biochem. J. 70 (1): 66–71. PMC 1196627. PMID 13584303. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1196627.
KEARNEY EB (1952). "The interaction of yeast flavokinase with riboflavin analogues". J. Biol. Chem. 194 (2): 747–54. PMID 14927668.
McCormick DB and Butler RC (1962). "Substrate specificity of liver flavokinase". Biochim. Biophys. Acta 65 (2): 326–332. doi:10.1016/0006-3002(62)91051-X.
Sandoval FJ, Roje S (2005). "An FMN hydrolase is fused to a riboflavin kinase homolog in plants". J. Biol. Chem. 280 (46): 38337–45. doi:10.1074/jbc.M500350200. PMID 16183635.
Solovieva IM, Tarasov KV, Perumov DA (Mosc). "Main physicochemical features of monofunctional flavokinase from Bacillus subtilis". B Biochemistry. (2): 177–81. PMID 12693963.
Solovieva IM, Kreneva RA, Leak DJ, Perumov DA (Pt 1). "The ribR gene encodes a monofunctional riboflavin kinase which is involved in regulation of the Bacillus subtilis riboflavin operon". Microbiology. 145: 67–73. doi:10.1099/13500872-145-1-67. PMID 10206712.

Metabolism of vitamins, coenzymes, and cofactors

Fat soluble vitamins

Vitamin A	Retinol binding protein

Vitamin E	Alpha-tocopherol transfer protein

Vitamin D	liver (Sterol 27-hydroxylase or CYP27A1) · renal (25-Hydroxyvitamin D₃ 1-alpha-hydroxylase or CYP27B1) · degradation (1,25-Dihydroxyvitamin D₃ 24-hydroxylase or CYP24A1)

Vitamin K	Vitamin K epoxide reductase

Water soluble vitamins

Thiamine (B₁)	Thiamine diphosphokinase

Niacin (B₃)	Indoleamine 2,3-dioxygenase · Formamidase

Pantothenic acid (B₅)	Pantothenate kinase

Folic acid (B₉)	Dihydropteroate synthase · Dihydrofolate reductase · Serine hydroxymethyltransferase Methylenetetrahydrofolate reductase

Vitamin B₁₂	MMAA · MMAB · MMACHC · MMADHC

Vitamin C	L-gulonolactone oxidase

Riboflavin (B₂)	Riboflavin kinase

Nonvitamin cofactors

Tetrahydrobiopterin	GTP cyclohydrolase I · 6-pyruvoyltetrahydropterin synthase · Sepiapterin reductase PCBD1 · PTS · QDPR

Molybdenum cofactor	MOCS1 · MOCS2 · MOCS3 · GPHN

M: NUT

cof, enz, met

noco, nuvi, sysi/epon, met

drug(A8/11/12)

This article incorporates text from the public domain Pfam and InterPro IPR015865

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Riboflavin kinase

This family represents the C-terminal region of the bifunctional riboflavin biosynthesis protein known as RibC in Bacillus subtilis. The RibC protein from Bacillus subtilis has both flavokinase and flavin adenine dinucleotide synthetase (FAD-synthetase) activities. RibC plays an essential role in the flavin metabolism [1]. This domain is thought to have kinase activity [2].

Literature references

Mack M, van Loon AP, Hohmann HP; , J Bacteriol 1998;180:950-955.: Regulation of riboflavin biosynthesis in Bacillus subtilis is affected by the activity of the flavokinase/flavin adenine dinucleotide synthetase encoded by ribC. PUBMED:9473052
Wang W, Kim R, Yokota H, Kim SH; , Proteins 2005;58:246-248.: Crystal structure of flavin binding to FAD synthetase of Thermotoga maritima. PUBMED:15468322

External database links

PANDIT:	PF01687
Pseudofam:	PF01687
SCOP:	1mrz
SYSTERS:	Flavokinase

This tab holds annotation information from the InterPro database.

InterPro entry IPR015865

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (EC), which converts it into FMN, and FAD synthetase (EC), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme [PUBMED:14580199], the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family [PUBMED:17049878]. The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases [PUBMED:12517446].

This entry represents the riboflavin kinase domains from bacteria and eukaryotes.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	riboflavin kinase activity (GO:0008531)
Biological process	riboflavin biosynthetic process (GO:0009231)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Alignment:	Seed (140) Full (3161) NCBI (2556) Metagenomics (2167)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (140) Full (3161) NCBI (2556) Metagenomics (2167)
Full length sequences	Full-sequences (3161)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed or full alignments.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_1221 (release 4.1)

Previous IDs:

FAD_Synth;

Type:

Domain

Author:

Bashton M, Bateman A, Mistry J, Eddy S

Number in seed:

140

Number in full:

3161

Average length of the domain:

127.00 aa

Average identity of full alignment:

36 %

Average coverage of the sequence by the domain:

40.80 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 15929002 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	19.6	19.6
Trusted cut-off	20.6	20.5
Noise cut-off	17.8	17.7

Model length:

125

Family (HMM) version:

12

Download:

download the raw HMM for this family

Species distribution

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

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We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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Interactions

There are 2 interactions for this family. More...

Flavokinase FAD_syn

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Flavokinase domain has been found. There are 23 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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Family: Flavokinase (PF01687)

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Summary: Riboflavin kinase

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Riboflavin kinase

[edit] Structure

[edit] References

[edit] Further reading

Riboflavin kinase

Literature references

External database links

InterPro entry IPR015865

Gene Ontology

Domain organisation

Alignments

Viewing

Downloading

View options

Formatting options

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures