Fig 7. Putative minimal elements underlying the emergence of cofactor-utilizing enzymes.

(A) The β1-α1–β2 segment that contains Gly-rich as well as the canonical β2-Asp/Glu interaction comprises the keystone of Rossmann enzymes [40,62] (taken from an NAD-dependent dehydrogenase, PDB 1LDN; see also S13 Fig). Indicated are the Gly-loop (glycines 27, 29, and 32, in yellow) and the canonical ribose ligating Asp at the tip of β2. (B) The P-loop comprises the keystone of the P-loop containing nucleotide triphosphate hydrolases. Shown is the β1-α1–β2 segment taken from a kinase (PDB 2AXN; in complex with ADP). The P-loop (yellow) stems from the first β-strand (β1) and into the first helix (H1). Note that the adenosine di-phosphate moiety, which is common to both cofactors, is bound in opposite directions (the β1-α1–β2 segments were aligned in the same direction).