Fig. 1

a Structural superposition of AHCY from the 9 organisms investigated here, using human (1LI4), mouse (5AXA) or lupin (3OND) crystal structures as templates. The blue loop is specific to plants and green algae; DZnep is shown in yellow, NAD⁺ in black. See also Supplementary Movie 1. b Docking simulation of human AHCY with DZnep, based on the 1LI4 crystal structure of human AHCY complexed with Neplanocin A, an analog of DZnep. The amino acids involved in DZnep binding are indicated with their position. See Supplementary Fig. 2 for docking simulations of DZnep to AHCY from other organisms. Red and green arrows are hydrogen bonds, yellow spheres are hydrophobic effects. The estimated free energy of binding for depicted DZnep docking conformation was −9.87 kcal/mol. c Discontinuous alignment of amino acids contributing to the binding of DZnep, using the human sequence as a reference and with sequence identities shown on the right. When amino acids are identical to human, a dot is shown in the alignment. The sequence logo on top is a graphical representation of the conservation of amino acids, with the consensus symbols below (* = fully conserved residue, : = conservation of strongly similar properties, . = conservation of weakly similar properties). The positions of selected conserved amino acids are given for the human sequence on top of the alignment. d Molecular docking simulations of AHCY with adenosine and DZnep showing comparable binding free energies in all organisms. Colors represent full sequence identities, relative to human.