184.108.40.206 - 3,4-dihydroxy-2-butanone-4-phosphate synthase
- DHBP synthase.
- L-3,4-dihydroxybutan-2-one-4-phosphate synthase.
D-ribulose 5-phosphate = (2S)-2-hydroxy-3-oxobutyl phosphate + formate + H(+)
L-3,4-Dihydroxy-2-butanone-4-phosphate synthase catalyses the conversion of ribulose 5-phosphate to L-3,4-dihydroxy-2-butanone-4-phosphate (DHBP) and formate in riboflavin biosynthesis. The proposed mechanism shares features with many enzymes, including the sugar isomerases.
A His-Asn dyad is central to the proposed mechanism of L-3,4-Dihydroxy-2-butanone-4-phosphate synthase. An initial enolisation step is mediated by Glu 185 acting as a general base to abstract the C3 proton in concert with the donation of a proton to the C2 carbonyl oxygen by His 147. Stabilisation of the enolate occurs via His 147, Asn 106 and Tyr 95. Dehydration is assisted by Cys 55 acting as a general acid. The enol is ketonised by an acid-base process with the C2 hydroxyl deprotonated by His 147 and a proton donated to C1 by Glu 185. A skeleton rearrangement is initiated by deprotonation of the C4 hydroxyl by Asp 30. Hydration by a magnesium-associated water follows with proton donation from His 147 yields the enolate intermediate, which binds to one magnesium only so that Glu 185 can deprotonate the C2 hydroxyl and the final product is generated by protonation by a magnesium-activated water.
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
Organism KM Value [mM] Substrate Comment Salmonella enterica subsp. enterica serovar Typhimurium 0.116 D-ribulose 5-phosphate 37°C, pH 7.5, Vmax: 199 nmol/min/mg Streptococcus pneumoniae 0.181 D-ribulose 5-phosphate pH 7.5, 37°C
Organism Temperature Range Comment Streptococcus pneumoniae 5 - 55 activity range, profile overview. Highest activity at 33°C, while at 30°C and 37°C, the activity decreases sharply to approximately 15-30% of the activity at 33°C
Organism pH Range Comment Mycobacterium tuberculosis 5 - 9 enzyme loses activity below pH 5.0 and above pH 9.0 Streptococcus pneumoniae 6 - 8 narrow optimum, no activity below or above, profile overview
- Evidence for the Chemical Mechanism of RibB (3,4-Dihydroxy-2-butanone 4-phosphate Synthase) of Riboflavin Biosynthesis.
- Structural basis for competitive inhibition of 3,4-dihydroxy-2-butanone-4-phosphate synthase from Vibrio cholerae.
- Synergy between polypyrrol and benzoic acid against antibiotic-resistant Salmonella spp.
- Inhibitors of riboflavin biosynthetic pathway enzymes as potential antibacterial drugs.
- [Cloning and characterization of a new antibacterial target, 3,4-dihydroxy-2-butanone-4-phosphate synthase].
- Role of riboflavin biosynthesis gene duplication and transporter in Aeromonas salmonicida virulence in marine teleost fish.
- Riboflavin accumulation and molecular characterization of cDNAs encoding bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase, lumazine synthase, and riboflavin synthase in different organs of Lycium chinense plant.
- The crystal structure reveals the molecular mechanism of bifunctional 3,4-dihydroxy-2-butanone 4-phosphate synthase/GTP cyclohydrolase II (Rv1415) from Mycobacterium tuberculosis.
- Structural basis for pH dependent monomer-dimer transition of 3,4-dihydroxy 2-butanone-4-phosphate synthase domain from Mycobacterium tuberculosis.
- Potential anti-bacterial drug target: structural characterization of 3,4-dihydroxy-2-butanone-4-phosphate synthase from Salmonella typhimurium LT2.
- Alternative models for two crystal structures of Candida albicans 3,4-dihydroxy-2-butanone 4-phosphate synthase.