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Catalytic Site Atlas

CSA LITERATURE entry for 1snn

E.C. name3,4-dihydroxy-2-butanone-4-phosphate synthase
SpeciesMethanococcus jannaschii ()
E.C. Number (IntEnz) 4.1.99.12
CSA Homologues of 1snn1pvw,1pvy,
CSA Entries With UniProtID Q60364
CSA Entries With EC Number 4.1.99.12
PDBe Entry 1snn
PDBSum Entry 1snn
MACiE Entry 1snn

Literature Report

IntroductionL-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 mechanism shares features with many enzymes, including the sugar isomerases.
MechansimA 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.
Reaction

Catalytic Sites for 1snn

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA185185macie:sideChainActs as a general acid/base in initialising enolisation by first abstracting a proton from C3 and later protonating C1, then deprotonating the C2 hydroxyl.
AsnA106106macie:sideChainActivates His 147, and also stabilises the enolate.
TyrA9595macie:sideChainStabilises the enolate.
AspA3030macie:sideChainInitiates skeleton rearrangement by deprotonating the C4 hydroxyl of the substrate.
SerA147147macie:sideChainActs as a general acid/base, and stabilises the enolate.
CysA5555macie:sideChainActs as a general acid to facilitate dehydration.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluB185185macie:sideChainActs as a general acid/base in initialising enolisation by first abstracting a proton from C3 and later protonating C1, then deprotonating the C2 hydroxyl.
AsnB106106macie:sideChainActivates His 147, and also stabilises the enolate.
TyrB9595macie:sideChainStabilises the enolate.
AspB3030macie:sideChainInitiates skeleton rearrangement by deprotonating the C4 hydroxyl of the substrate.
SerB147147macie:sideChainActs as a general acid/base, and stabilises the enolate.
CysB5555macie:sideChainActs as a general acid to facilitate dehydration.

Literature References

Notes:Magnesium is also essential for catalysis. However as it is not in the PDB file it cannot be annotated. Two magnesium ions are required for catalysis in the active site.
Liao DI
Structural definition of the active site and catalytic mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase.
Biochemistry 2002 41 1795-1806
PubMed: 11827524
Steinbacher S
Structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase from Methanococcus jannaschii in complex with divalent metal ions and the substrate ribulose 5-phosphate: implications for the catalytic mechanism.
J Biol Chem 2003 278 42256-42265
PubMed: 12904291
Fischer M
Biosynthesis of riboflavin in archaea studies on the mechanism of 3,4-dihydroxy-2-butanone-4-phosphate synthase of Methanococcus jannaschii.
J Biol Chem 2002 277 41410-41416
PubMed: 12200440
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