6,7-dimethyl-8-ribityllumazine synthase

 

Riboflavin is biosynthesised in plants, fungi and certain microorganisms; as animals lack the necessary enzymes to produce this vitamin, they acquire it from dietary sources. The penultimate step in the biosynthesis of riboflavin (vitamin B2) involves the condensation of 3,4-dihydroxy-2-butanone 4-phosphate with 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which is catalysed by 6,7-dimethyl-8-ribityllumazine synthase (lumazine synthase).

 

Reference Protein and Structure

Sequence
P11998 UniProt (2.5.1.78) IPR034964 (Sequence Homologues) (PDB Homologues)
Biological species
Bacillus subtilis subsp. subtilis str. 168 (Bacteria) Uniprot
PDB
1rvv - SYNTHASE/RIBOFLAVIN SYNTHASE COMPLEX OF BACILLUS SUBTILIS (2.4 Å) PDBe PDBsum 1rvv
Catalytic CATH Domains
3.40.50.960 CATHdb (see all for 1rvv)
Click To Show Structure

Enzyme Reaction (EC:2.5.1.78)

(2S)-2-hydroxy-3-oxobutyl phosphate(2-)
CHEBI:58830ChEBI
+
5-amino-6-(D-ribitylamino)uracil
CHEBI:15934ChEBI
→
6,7-dimethyl-8-(1-D-ribityl)lumazine(1-)
CHEBI:58201ChEBI
+
water
CHEBI:15377ChEBI
+
hydron
CHEBI:15378ChEBI
+
hydrogenphosphate
CHEBI:43474ChEBI
Alternative enzyme names: Lumazine synthase, 6,7-dimethyl-8-ribityllumazine synthase 2, 6,7-dimethyl-8-ribityllumazine synthase 1, Lumazine synthase 2, Lumazine synthase 1, Type I lumazine synthase, Type II lumazine synthase, RIB4, MJ0303, RibH, PblS, MbtLS, RibH1 protein, RibH2 protein, RibH1, RibH2,

Enzyme Mechanism

Introduction

It has been proposed that the first step of the mechanism involves the formation of a Schiff base intermediate between the two substrates. The position 7 hydrogen of the intermediate is removed by His88, which facilitates the loss of the phosphate group. The intermediate then undergoes tautomerisation and rotation of the enol motif. This positions the carbonyl group for the final ring closure.

Catalytic Residues Roles

UniProt PDB* (1rvv)
His88 His88A Acts as a general acid/base. proton shuttle (general acid/base)
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Fischer M et al. (2003), J Mol Biol, 326, 783-793. Enzyme catalysis via control of activation entropy: site-directed mutagenesis of 6,7-dimethyl-8-ribityllumazine synthase. PMID:12581640.
  2. Gerhardt S et al. (2002), J Mol Biol, 318, 1317-1329. The Structural Basis of Riboflavin Binding to Schizosaccharomyces pombe 6,7-Dimethyl-8-ribityllumazine Synthase. DOI:10.1016/s0022-2836(02)00116-x. PMID:12083520.
  3. Zhang X et al. (2001), J Mol Biol, 306, 1099-1114. X-ray structure analysis and crystallographic refinement of lumazine synthase from the hyperthermophile Aquifex aeolicus at 1.6 Å resolution: determinants of thermostability revealed from structural comparisons. DOI:10.1006/jmbi.2000.4435. PMID:11237620.
  4. Meining W et al. (2000), J Mol Biol, 299, 181-197. The atomic structure of pentameric lumazine synthase from Saccharomyces cerevisiae at 1.85 Å resolution reveals the binding mode of a phosphonate intermediate analogue. DOI:10.1006/jmbi.2000.3742. PMID:10860731.
  5. Kis K et al. (1995), Biochemistry, 34, 2883-2892. Biosynthesis of riboflavin. Studies on the reaction mechanism of 6,7-dimethyl-8-ribityllumazine synthase. PMID:7893702.
  6. Ritsert K et al. (1995), J Mol Biol, 253, 151-167. Studies on the lumazine synthase/riboflavin synthase complex of Bacillus subtilis: crystal structure analysis of reconstituted, icosahedral beta-subunit capsids with bound substrate analogue inhibitor at 2.4 A resolution. DOI:10.1006/jmbi.1995.0542. PMID:7473709.

Step 1.

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Catalytic Residues Roles

Residue Roles
His88A proton shuttle (general acid/base)

Chemical Components

Step 1.

Contributors

Christian Drew, Craig Porter, Gemma L. Holliday