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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Enzyme: riboflavin synthase

Gene: ribC Accession Numbers: EG11406 (MetaCyc), b1662, ECK1658

Synonyms: ribE

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of riboflavin synthase = [RibC]3

Summary:
Riboflavin synthase catalyzes the final step in riboflavin biosynthesis, the formation of the carbocyclic ring of riboflavin by dismutation of 6,7-dimethyl-8-ribityllumazine. No homolog of this enzyme exists in humans, and it is therefore an attractive target for antimicrobial agents against microbes that are dependent on endogenous synthesis of riboflavin. Inhibitors of riboflavin synthase with antibiotic activity have been developed, e.g. [Zhao09].

A recombinant N-terminal domain fragment dimerizes and is able to bind riboflavin [Eberhardt01]. Catalytically relevant amino acid residues have been identified by mutagenesis [Illarionov01, Lee07a]. A kinetically competent reaction intermediate has been identified [Illarionov01a], and the enzyme kinetics have been studied under single turnover conditions [Illarionov03, Illarionov05]. A new, simpler mechanism for formation of the pentacyclic reaction intermediate via hydryde transfer has been proposed [Kim10a].

Riboflavin synthase is a homotrimer in solution [Eberhardt96]. Solution and crystal structures of N-terminal riboflavin-binding domain fragments and the homotrimeric enzyme have been solved. Each subunit consists of two similarly-folding domains [Meining98, Truffault01, Liao01, Meining03].

ribC is an essential gene [Baba06].

Review: [Fischer05]

Locations: cytosol

Map Position: [1,740,625 <- 1,741,266]

Molecular Weight of Polypeptide: 23.445 kD (from nucleotide sequence)

Molecular Weight of Multimer: 70 kD (experimental) [Eberhardt96]

pI: 5.97

Unification Links: ASAP:ABE-0005557 , CGSC:11923 , DIP:DIP-47865N , EchoBASE:EB1378 , EcoGene:EG11406 , EcoliWiki:b1662 , ModBase:P0AFU8 , OU-Microarray:b1662 , PortEco:ribC , PR:PRO_000023753 , Pride:P0AFU8 , Protein Model Portal:P0AFU8 , RefSeq:NP_416179 , RegulonDB:EG11406 , SMR:P0AFU8 , String:511145.b1662 , Swiss-Model:P0AFU8 , UniProt:P0AFU8

Relationship Links: InterPro:IN-FAMILY:IPR001783 , InterPro:IN-FAMILY:IPR017938 , InterPro:IN-FAMILY:IPR023366 , InterPro:IN-FAMILY:IPR026017 , Panther:IN-FAMILY:PTHR21098 , PDB:Structure:1HZE , PDB:Structure:1I8D , PDB:Structure:1I18 , PDB:Structure:1PKV , Pfam:IN-FAMILY:PF00677 , Prosite:IN-FAMILY:PS51177

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0009231 - riboflavin biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, GOA01a, Eberhardt96]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0004746 - riboflavin synthase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Eberhardt96]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [GOA01a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers riboflavin

Credits:
Created in EcoCyc 23-Mar-2006 by Keseler I , SRI International
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: riboflavin synthase

Synonyms: 6,7-dimethyl-8-(1-D-ribityl)lumazine:6,7-dimethyl-8- (1-D-ribityl)lumazine 2,3-butanediyltransferase

EC Number: 2.5.1.9

2 6,7-dimethyl-8-(1-D-ribityl)lumazine + H+ <=> 5-amino-6-(D-ribitylamino)uracil + riboflavin

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

In Pathways: flavin biosynthesis I (bacteria and plants)

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Kinetic Parameters:

Substrate
kcat (sec-1)
Citations
6,7-dimethyl-8-(1-D-ribityl)lumazine
0.27
[Illarionov05, BRENDA14]

pH(opt): 7 [BRENDA14, PLAUT63]


Sequence Features

Feature Class Location Citations Comment
Repeat 1 -> 97
[UniProt09]
UniProt: Lumazine-binding 1;
Protein-Segment 4 -> 6
[UniProt12]
UniProt: Substrate binding; Sequence Annotation Type: region of interest.
Protein-Segment 48 -> 50
[UniProt12]
UniProt: Substrate binding; Sequence Annotation Type: region of interest.
Protein-Segment 62 -> 67
[UniProt12]
UniProt: Substrate binding; Sequence Annotation Type: region of interest.
Repeat 98 -> 195
[UniProt09]
UniProt: Lumazine-binding 2;

History:
1/26/1998 (pkarp) Merged genes G7993/ribE and EG11406/ribC


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Eberhardt01: Eberhardt S, Zingler N, Kemter K, Richter G, Cushman M, Bacher A (2001). "Domain structure of riboflavin synthase." Eur J Biochem 268(15);4315-23. PMID: 11488927

Eberhardt96: Eberhardt S, Richter G, Gimbel W, Werner T, Bacher A (1996). "Cloning, sequencing, mapping and hyperexpression of the ribC gene coding for riboflavin synthase of Escherichia coli." Eur J Biochem 242(3);712-9. PMID: 9022701

Fischer05: Fischer M, Romisch W, Illarionov B, Eisenreich W, Bacher A (2005). "Structures and reaction mechanisms of riboflavin synthases of eubacterial and archaeal origin." Biochem Soc Trans 33(Pt 4);780-4. PMID: 16042598

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Illarionov01: Illarionov B, Kemter K, Eberhardt S, Richter G, Cushman M, Bacher A (2001). "Riboflavin synthase of Escherichia coli. Effect of single amino acid substitutions on reaction rate and ligand binding properties." J Biol Chem 276(15);11524-30. PMID: 11278450

Illarionov01a: Illarionov B, Eisenreich W, Bacher A (2001). "A pentacyclic reaction intermediate of riboflavin synthase." Proc Natl Acad Sci U S A 98(13);7224-9. PMID: 11404482

Illarionov03: Illarionov B, Haase I, Bacher A, Fischer M, Schramek N (2003). "Presteady state kinetic analysis of riboflavin synthase." J Biol Chem 278(48);47700-6. PMID: 14504292

Illarionov05: Illarionov B, Haase I, Fischer M, Bacher A, Schramek N (2005). "Pre-steady-state kinetic analysis of riboflavin synthase using a pentacyclic reaction intermediate as substrate." Biol Chem 386(2);127-36. PMID: 15843156

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Kim10a: Kim RR, Illarionov B, Joshi M, Cushman M, Lee CY, Eisenreich W, Fischer M, Bacher A (2010). "Mechanistic insights on riboflavin synthase inspired by selective binding of the 6,7-dimethyl-8-ribityllumazine exomethylene anion." J Am Chem Soc 132(9);2983-90. PMID: 20143812

Lee07a: Lee CY, Illarionov B, Woo YE, Kemter K, Kim RR, Eberhardt S, Cushman M, Eisenreich W, Fischer M, Bacher A (2007). "Ligand binding properties of the N-terminal domain of riboflavin synthase from Escherichia coli." J Biochem Mol Biol 40(2);239-46. PMID: 17394775

Liao01: Liao DI, Wawrzak Z, Calabrese JC, Viitanen PV, Jordan DB (2001). "Crystal structure of riboflavin synthase." Structure 9(5);399-408. PMID: 11377200

Meining03: Meining W, Eberhardt S, Bacher A, Ladenstein R (2003). "The structure of the N-terminal domain of riboflavin synthase in complex with riboflavin at 2.6A resolution." J Mol Biol 331(5);1053-63. PMID: 12927541

Meining98: Meining W, Tibbelin G, Ladenstein R, Eberhardt S, Fischer M, Bacher A (1998). "Evidence for local 32 symmetry in homotrimeric riboflavin synthase of Escherichia coli." J Struct Biol 121(1);53-60. PMID: 9573620

PLAUT63: PLAUT GW (1963). "Studies on the nature of the enzymic conversion of 6,7-dimethyl-8-ribityllumazine to riboflavin." J Biol Chem 238;2225-43. PMID: 13944007

Truffault01: Truffault V, Coles M, Diercks T, Abelmann K, Eberhardt S, Luttgen H, Bacher A, Kessler H (2001). "The solution structure of the N-terminal domain of riboflavin synthase." J Mol Biol 309(4);949-60. PMID: 11399071

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt12: UniProt Consortium (2012). "UniProt version 2012-09 released on 2012-09-12 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Zhao09: Zhao Y, Bacher A, Illarionov B, Fischer M, Georg G, Ye QZ, Fanwick PE, Franzblau SG, Wan B, Cushman M (2009). "Discovery and development of the covalent hydrates of trifluoromethylated pyrazoles as riboflavin synthase inhibitors with antibiotic activity against Mycobacterium tuberculosis." J Org Chem 74(15);5297-303. PMID: 19545132


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, biocyc13.