Structural and Functional Consequences of Phosphate-Arsenate Substitutions in Selected Nucleotides: DNA, RNA, and ATP

Abstract

A recent finding of a bacterial strain (GFAJ-1) that can rely on arsenic instead of phosphorus raised the questions of if and how arsenate can replace phosphate in biomolecules that are essential to sustain cell life. Apart from questions related to chemical stability, there are those of the structural and functional consequences of phosphate-arsenate substitutions in vital nucleotides in GFAJ1-like cells. In this study we selected three types of molecules (ATP/ADP as energy source and replication regulation; DNA-protein complexes for DNA replication and transcription initiation; and a tRNA-protein complex and ribosome for protein synthesis) to computationally probe if arsenate nucleotides can retain the structural and functional features of phosphate nucleotides. We further compared the experimental EXAFS spectra of the arsenic bacteria with theoretical EXAFS spectra for arsenate DNA and rRNA. Our results demonstrate that while it is possible that dried GFAJ-1 cells contain linear arsenate DNA, the arsenate 70S ribosome does not contribute to the main arsenate depository in the GFAJ-1 cell. Our study indicates that evolution has optimized the inter-relationship between proteins and DNA/RNA, which requires overall changes at the molecular and systems biology levels when replacing phosphate by arsenate.