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Catalytic Site Atlas

CSA LITERATURE entry for 2a0n

E.C. name
SpeciesThermotoga maritima (Bacteria)
E.C. Number (IntEnz) 4.1.3.-
CSA Homologues of 2a0nThere are 12 Homologs
CSA Entries With UniProtID
CSA Entries With EC Number 4.1.3.-
PDBe Entry 2a0n
PDBSum Entry 2a0n
MACiE Entry 2a0n

Literature Report

IntroductionThe tHisF subunit of Thermotoga maritima imidazole glycerol phosphate (ImGP) synthase catalyses the reaction of N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide (PRFAR) with ammonia to form an imine, loss of 5-aminoimidazole-4-carboxamide ribotide (AICAR), and the subsequent cyclisation to form ImGP. ImGP and AICAR are used in histidine and purine biosynthesis respectively.
Ammonia is delivered to the active site directly from an associated subunit tHisH which hydrolyses glutamine to glutamate.
MechansimThe reaction of PRFAR and ammonia moves through a series of imine intermediates. A nucleophilic ammonia molecule attacks the carbonyl group next to the phosphoglycerol, with subsequent imine formation. Water then hydrolyses the imine group linking the ribosephosphate and phosphoglycerol moieties, separating the substrate into a formamide and AICAR. These steps may be catalysed solely by enzyme binding, or be catalysed by the Asp 11 and Asp 130 residues necessary for the cyclisation steps.
Asp 130 deprotonates -CH2- as the imine group intramolecularly attacks the electrophilic formamide group through the imine's nitrogen, with a protonated Asp 11 supplying the proton for the carbonyl oxygen atom. The resulting intermediate is cyclic with adjacent -C(OH)- and -NH- groups. Asp 11 can deprotonate -NH- leading to C=N imine bond formation, with the OH leaving as water with the proton from Asp 130.

Catalytic Sites for 2a0n

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA1111macie:sideChainAsp 11 deprotonates the -CH2- group of the formamide intermediate. This occurs simultaneously with nucleophilic attack of the imine on the formamide. Asp 11 is now protonated and can act as a general acid to the hydroxy group, giving water as a leaving group.
AspA130130macie:sideChainAsp 130 is protonated and can act as a general acid to the formamide's carbonyl group to give the hydroxyl of the next intermediate. Asp 130 can then deprotonate the -NH- group to form the imine bond of the imidazole product.

Literature References

Notes:The exact mechanism of this complex reaction is not precisely known, but Asp 11 and Asp 130 are definitely needed for catalysis.
Beismann-Driemeyer S
Imidazole glycerol phosphate synthase from Thermotoga maritima. Quaternary structure, steady-state kinetics, and reaction mechanism of the bienzyme complex.
J Biol Chem 2001 276 20387-20396
PubMed: 11264293
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