Structural highlights
Function
[BLUB_RHIME] Involved in the biosynthesis of cobalamin (vitamin B12). Catalyzes the oxidative fragmentation and contraction of the isoalloxazine heterocycle and the cleavage of the ribityl tail of FMN(2) to form 5,6-dimethylbenzimidazole (DMB) and D-erythrose 4-phosphate (E4P). NAD(P)H is only required initially to reduce FMN and oxygen drives the oxidative fragmentation.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Vitamin B12 (cobalamin) is among the largest known non-polymeric natural products, and the only vitamin synthesized exclusively by microorganisms. The biosynthesis of the lower ligand of vitamin B(12), 5,6-dimethylbenzimidazole (DMB), is poorly understood. Recently, we discovered that a Sinorhizobium meliloti gene, bluB, is necessary for DMB biosynthesis. Here we show that BluB triggers the unprecedented fragmentation and contraction of the bound flavin mononucleotide cofactor and cleavage of the ribityl tail to form DMB and D-erythrose 4-phosphate. Our structural analysis shows that BluB resembles an NAD(P)H-flavin oxidoreductase, except that its unusually tight binding pocket accommodates flavin mononucleotide but not NAD(P)H. We characterize crystallographically an early intermediate along the reaction coordinate, revealing molecular oxygen poised over reduced flavin. Thus, BluB isolates and directs reduced flavin to activate molecular oxygen for its own cannibalization. This investigation of the biosynthesis of DMB provides clarification of an aspect of vitamin B12 that was otherwise incomplete, and may contribute to a better understanding of vitamin B12-related disease.
BluB cannibalizes flavin to form the lower ligand of vitamin B12.,Taga ME, Larsen NA, Howard-Jones AR, Walsh CT, Walker GC Nature. 2007 Mar 22;446(7134):449-53. PMID:17377583[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Campbell GR, Taga ME, Mistry K, Lloret J, Anderson PJ, Roth JR, Walker GC. Sinorhizobium meliloti bluB is necessary for production of 5,6-dimethylbenzimidazole, the lower ligand of B12. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4634-9. Epub 2006 Mar 1. PMID:16537439
- ↑ Taga ME, Larsen NA, Howard-Jones AR, Walsh CT, Walker GC. BluB cannibalizes flavin to form the lower ligand of vitamin B12. Nature. 2007 Mar 22;446(7134):449-53. PMID:17377583 doi:10.1038/nature05611
- ↑ Taga ME, Larsen NA, Howard-Jones AR, Walsh CT, Walker GC. BluB cannibalizes flavin to form the lower ligand of vitamin B12. Nature. 2007 Mar 22;446(7134):449-53. PMID:17377583 doi:10.1038/nature05611
