English: Overall structure of a viral RdRP. (A) Ribbon representation of a typical picornaviral RdRP (model from the cardiovirus EMCV 3Dpol, PDB id. 4NZ0). The seven conserved motifs are indicated in different colours: motif A, red; motif B, green; motif C, yellow; motif D, sand; motif E, cyan; motif F, blue; motif G, pink; (B) Lateral view of a surface representation of the enzyme (grey) that has been cut to expose the three channels that are the entry and exit sites of the different substrates and reaction products. The structural elements that support motifs A–G are also shown as ribbons. This panel also shows the organization of the palm sub-domain with motif A shown in two alternative conformations: the standard conformation (PDB id. 4NZ0) found in the apo-form of most crystallized 3Dpol proteins and the altered conformation found int the tetragonal crystal form of the EMCV enzyme (PDB id. 4NYZ). The alterations affect mainly Asp240, the amino acid in charge of incoming ribonucleotide triphosphate (rNTP) selection, and the neighboring Phe239 that move ~10 Å away from its position in the enzyme catalytic cavity directed towards the entrance of the nucleotide channel, approaching to motif F; (C) Close up of the structural superimposition of the two alternative conformations of the EMCV motif A