| Identification |
|---|
| HMDB Protein ID
| HMDBP13881 |
| Secondary Accession Numbers
| None |
| Name
| 6,7-dimethyl-8-ribityllumazine synthase 2 |
| Synonyms
|
- DMRL synthase 2
- LS 2
- Lumazine synthase 2
- BLS
- Type II lumazine synthase
|
| Gene Name
| RIBH2 |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| Catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2-butanone 4-phosphate (PubMed:10482294, PubMed:16165152, PubMed:20195542). This is the penultimate step in the biosynthesis of riboflavin. The isozyme RibH2 but not RibH1 is essential for Brucella intracellular survival and replication inside macrophages or in mice (PubMed:20195542). Displays low catalytic activity in comparison with the isozyme RibH1 (PubMed:16165152). Is a highly immunogenic protein (PubMed:14500496). Activates dendritic cells (DCs) in vitro, increasing the levels of costimulatory molecules and the secretion of proinflammatory cytokines, and recruits DCs, B cells and CD8+ T cells in vivo, both effects in a TLR4-dependent manner (PubMed:16455994). Induces the cross presentation of covalently attached peptides and generates a strong and long-lasting humoral immune response without adjuvants; TLR4 signaling is necessary for the induction of the cytotoxic response but not for antigen cross presentation (PubMed:23029192). Elicits a TLR4-mediated protective response against B16 melanoma in mice, slowing tumor growth and prolonging mice survival (PubMed:25973756). |
| Pathways
|
- Biosynthesis of cofactors
- Biosynthesis of secondary metabolites
- riboflavin biosynthesis
- Riboflavin metabolism
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| pathogenesis |
| riboflavin biosynthetic process |
| Cellular Component |
| cytoplasm |
| riboflavin synthase complex |
| Molecular Function |
| 6,7-dimethyl-8-ribityllumazine synthase activity |
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| Not Available |
| Locus
| Not Available |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| 158 |
| Molecular Weight
| 17355.785 |
| Theoretical pI
| 7.118 |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| Q2YKV1 |
| UniProtKB/Swiss-Prot Entry Name
| RISB2_BRUA2 |
| PDB IDs
|
|
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Chain PS, Comerci DJ, Tolmasky ME, Larimer FW, Malfatti SA, Vergez LM, Aguero F, Land ML, Ugalde RA, Garcia E: Whole-genome analyses of speciation events in pathogenic Brucellae. Infect Immun. 2005 Dec;73(12):8353-61. doi: 10.1128/IAI.73.12.8353-8361.2005. [PubMed:16299333 ]
- Goldbaum FA, Velikovsky CA, Baldi PC, Mortl S, Bacher A, Fossati CA: The 18-kDa cytoplasmic protein of Brucella species --an antigen useful for diagnosis--is a lumazine synthase. J Med Microbiol. 1999 Sep;48(9):833-839. doi: 10.1099/00222615-48-9-833. [PubMed:10482294 ]
- Velikovsky CA, Goldbaum FA, Cassataro J, Estein S, Bowden RA, Bruno L, Fossati CA, Giambartolomei GH: Brucella lumazine synthase elicits a mixed Th1-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used. Infect Immun. 2003 Oct;71(10):5750-5. doi: 10.1128/IAI.71.10.5750-5755.2003. [PubMed:14500496 ]
- Zylberman V, Craig PO, Klinke S, Braden BC, Cauerhff A, Goldbaum FA: High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase. J Biol Chem. 2004 Feb 27;279(9):8093-101. doi: 10.1074/jbc.M312035200. Epub 2003 Dec 1. [PubMed:14660615 ]
- Zylberman V, Klinke S, Haase I, Bacher A, Fischer M, Goldbaum FA: Evolution of vitamin B2 biosynthesis: 6,7-dimethyl-8-ribityllumazine synthases of Brucella. J Bacteriol. 2006 Sep;188(17):6135-42. doi: 10.1128/JB.00207-06. [PubMed:16923880 ]
- Berguer PM, Mundinano J, Piazzon I, Goldbaum FA: A polymeric bacterial protein activates dendritic cells via TLR4. J Immunol. 2006 Feb 15;176(4):2366-72. doi: 10.4049/jimmunol.176.4.2366. [PubMed:16455994 ]
- Bonomi HR, Marchesini MI, Klinke S, Ugalde JE, Zylberman V, Ugalde RA, Comerci DJ, Goldbaum FA: An atypical riboflavin pathway is essential for Brucella abortus virulence. PLoS One. 2010 Feb 25;5(2):e9435. doi: 10.1371/journal.pone.0009435. [PubMed:20195542 ]
- Rossi AH, Farias A, Fernandez JE, Bonomi HR, Goldbaum FA, Berguer PM: Brucella spp. Lumazine Synthase Induces a TLR4-Mediated Protective Response against B16 Melanoma in Mice. PLoS One. 2015 May 14;10(5):e0126827. doi: 10.1371/journal.pone.0126827. eCollection 2015. [PubMed:25973756 ]
- Braden BC, Velikovsky CA, Cauerhff AA, Polikarpov I, Goldbaum FA: Divergence in macromolecular assembly: X-ray crystallographic structure analysis of lumazine synthase from Brucella abortus. J Mol Biol. 2000 Apr 14;297(5):1031-6. doi: 10.1006/jmbi.2000.3640. [PubMed:10764570 ]
- Klinke S, Zylberman V, Vega DR, Guimaraes BG, Braden BC, Goldbaum FA: Crystallographic studies on decameric Brucella spp. Lumazine synthase: a novel quaternary arrangement evolved for a new function? J Mol Biol. 2005 Oct 14;353(1):124-37. doi: 10.1016/j.jmb.2005.08.017. [PubMed:16165152 ]
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