Survey of ribose ring pucker of signaling nucleosides and nucleotides

The ribose of protein-bound nucleosides and nucleotides displays preferred conformations (usually either North or South), which can be exploited to design enhanced analogs having chemically fixed conformations. We introduce a computational protocol for assembling data from the protein database (PDB) on the ribose and ribose-like conformation of small molecule ligands when complexed with purinergic signaling proteins (including receptors, enzymes and transporters, and related intracellular pathways). Some targets prefer exclusively North (adenosine and P2Y₁ receptors, CD73, adenosine kinase ATP/ADP-binding site, adenosine deaminase), others prefer South (P2Y₁₂ receptor, E-NTPDase2) or East (adenosine kinase substrates), while others (P2XRs) allow various conformations.