Preiner, Martina; Pereira, Delfina Henriques; Xie, Xiulan; Subrati, Zainab; Beyazay, Tuğçe; Paczia, Nicole; Belz, Jürgen; Volz, Kerstin; Tüysüz, Harun

DOI:

Abstract

Many cofactors share a molecular structure - - that otherwise occurs in nucleic acids. The presence of in cofactors has presented an evolutionary puzzle. Is it a biochemical ‘handle’ that allows proteins to bind the cofactor more tightly, or is it a relic from a time when cofactors arose from the building blocks of genes? Using the example of (NAD), we find a surprising and previously unknown property of its (AMP) handle. Reduction experiments with hydrogen gas (H2) on mineral surfaces show that the handle-free nicotinamide mononucleotide (NMN) overreduces quickly, while NAD gets reduced specifically. The AMP handle allows NAD to function in a hydrothermal, mineral-based setting, indicating that it is a form of protection against a harsh chemical environment in which biochemistry and life arose. Our findings uncover a specific functional role for the AMP moiety of NAD under environmental conditions capable of nonenzymatic NAD reduction, thereby identifying a structural element of a redox cofactor that is older than the enzymes that use it.

Keywords

adenosine cofactors ; hydrogen ; emergence of life ; mineral catalysis ; protometabolism

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