LYS70 of E. coli Quinolinate Phosphoribosyltransferase Is Protected from Chemical Modification by Formation of an Inhibitor Complex.

Gaur, Rajula; Roberts, Tanesha; Calvo, K. C.

doi:10.2174/092986606775101652

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“…In both prokaryotes and eukaryotes, quinolinate phosphoribosyl transferase (QPRTase), a type II PRTase, is an essential enzyme that lies on the de novo pathway for nicotinamide adenine dinucleotide (NAD) biosynthesis. − The enzyme is specific in catalyzing the reaction of quinolinic acid (QA) and 5′-phosphoribosyl-1′-pyrophosphate (PRPP) in the presence of a magnesium cation to form pyrophosphate, carbon dioxide, and nicotinic acid mononucleotide (NAMN, Scheme ). − …”

Section: Introductionmentioning

confidence: 99%

Theoretical Studies of the Quinolinic Acid to Nicotinic Acid Mononucleotide Transformation

Rozenberg

Lee

2008

J. Org. Chem.

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Quinolinate phosphoribosyl transferase (QPRTase) is an essential enzyme that catalyzes the transformation of quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN), a key step on the de novo pathway for nicotinamide adenine dinucleotide (NAD) biosynthesis. We describe herein a theoretical study of the intrinsic energetics associated with the possible mechanistic pathways by which QA forms NAMN. Our main interest is in probing the decarboxylation step, which is intriguing since the product is a vinylic anion, not unlike the reaction catalyzed by orotidine 5'-monophosphate (OMP) decarboxylase, an enzyme whose mechanism is under fierce debate. Our calculations indicate that a path involving a quinolinic acid mononucleotide (QAMN) intermediate is the most energetically attractive, favoring decarboxylation. We also find that the monocarboxylate form of QAMN will decarboxylate much more favorably energetically than will the dicarboxylate form of QAMN. Furthermore, our calculations indicate that decarboxylation is not a likely first step; the substrate in such a mechanism would prefer to decarboxylate at the C3 position, not the desired C2 position. We also discuss our results in the context of existing experimental data.

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