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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1qpr

E.C. namenicotinate-nucleotide diphosphorylase (carboxylating)
SpeciesMycobacterium tuberculosis (Bacteria)
E.C. Number (IntEnz) 2.4.2.19
CSA Homologues of 1qprThere are 28 Homologs
CSA Entries With UniProtID O06594
CSA Entries With EC Number 2.4.2.19
PDBe Entry 1qpr
PDBSum Entry 1qpr
MACiE Entry M0008

Literature Report

IntroductionQuinolinic acid phosphoribosyltransferase (QAPRTase) is required for the de novo biosynthesis of NAD in both prokaryotes and eukaryotes. The enzyme catalyses the reaction between quinolinic acid (QA) and 5-phosphoribosyl-1-pyrophosphate (PRPP), to yield nicotinic acid mononucleotide (NAMN), pyrophosphate and CO2, the latter resulting from decarboxylation at position 2 of the quinolinate ring.
MechansimPhosphoribosyl transfer has been proposed to proceed via a unimolecular nucleophilic substitution (SN1 reaction) involving an oxycarbonium-like intermediate. In a rate-limiting step, the pyrophosphate group of PRPP is protonated and cleaved to yield an oxycarbonium of ribosylphosphate. The formation of the anticipated intermediate may be facilitated by the electron-withdrawing power of the metal ions and the C3-exo pucker of the ribosyl ring. Subsequently, the nucleophilic N1 of QA combines with the oxycarbonium in a diffusion-controlled reaction to form quinolinic acid mononucleotide (QAMN) [2].
QAPRTase has been grouped with nine enzymes, (phosphoribosyltransferases, PRTases) that catalyses chemically similar phosphoribosyl transfer reactions using the substrate PRPP. The PRTases are involved in de novo and salvage reactions of nucleotide synthesis, as well as in histidine and tryptophan biosynthesis [1]. To date, crystal structures have been determined for several PRTase enzymes and all show a common 'PRTase fold' (the 'type I' fold) composed of a central beta sheet, of five beta strands, surrounded by alpha helices. The fold contains a common recognition motif of thirteen residues which is critical for PRPP binding and catalysis. However, as these enzymes (type II) lack the type I PRPP-binding motif and has TIM barrel-like structure, it becomes possible that thre might be at least two different types of PRTase fold [1].
Reaction

Catalytic Sites for 1qpr

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA201201macie:sideChain
LysA140140macie:sideChain
AspA222222macie:sideChain
ArgB105105macie:sideChain

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA105105macie:sideChain
GluB201201macie:sideChain
LysB140140macie:sideChain
AspB222222macie:sideChain

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgC105105macie:sideChain
GluD201201macie:sideChain
LysD140140macie:sideChain
AspD222222macie:sideChain

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgD105105macie:sideChain
GluC201201macie:sideChain
LysC140140macie:sideChain
AspC222222macie:sideChain

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluF201201macie:sideChain
LysF140140macie:sideChain
AspF222222macie:sideChain
ArgE105105macie:sideChain

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgF105105macie:sideChain
GluE201201macie:sideChain
LysE140140macie:sideChain
AspE222222macie:sideChain

Literature References

Notes:
Eads JC
A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase.
Structure 1997 5 47-58
PubMed: 9016724
Sharma V
Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target.
Structure 1998 6 1587-1599
PubMed: 9862811
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