Abstract

An Enzymatic Palimpsest

Highlights

  • According to the Compact Oxford English Dictionary, a palimpsest is “a parchment or other surface on which writing has been applied over earlier writing which has been erased.” Scholars are often able to decipher the earlier writing present on palimpsests by using chemical and imaging techniques

  • In a new study of a key enzyme that’s involved in the biosynthesis of the guanine nucleotides, inosine 5’-monophosphate dehydrogenase (IMPDH), Donghong Min and her colleagues uncovered an enzymatic palimpsest, an ancient chemical-bond–cleaving mechanism that lay obscured by the mechanism currently used by modern IMPDH

  • IMPDH binds to the substrate inosine 5’-monophosphate (IMP) and to the cofactor NAD+ and transfers a proton and two electrons from IMP to NAD+. This produces NADH and the intermediate product E-XMP*, which is linked to the residue cysteine 319 (Cys319) on IMPDH

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Summary

Introduction

According to the Compact Oxford English Dictionary, a palimpsest is “a parchment or other surface on which writing has been applied over earlier writing which has been erased.” Scholars are often able to decipher the earlier writing present on palimpsests by using chemical and imaging techniques. Some multipurpose enzymes do this by tethering their molecular substrate to a flexible “linker” of amino acids, which swings the substrate from one enzymatic active site to another. IMPDH catalyzes two very different chemical reactions at a single active site.

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