Fig. 4: Detailed structural determinants underlying the nucleotide cycling and dynamic landscape of the E5 helicase.

a The structural superimposition of the AAA+ domains between MPXV E5 (in green) and BPV E1 (in gray, PDB Code 2GXA). The Nucleotide sensor motif is highlighted. The surface of the nucleotide binding pockets of MPXV E5 (left) and BPV E1 (right) are shown, with the nucleotides bound inside shown as sticks. b Details of nucleotide-protein interactions (left) and cis-trans interaction (right) at representative ATP stable sites. Key amino acids involved in polar interactions (depicted with yellow dotted lines) are shown as sticks and labeled. c Comparisons of nucleotide binding pockets containing the nucleotide substrate in different hydrolysis states reveals a gradually increasing distance between tran- and cis-protomers. d The conformational difference (black arrow) of the Walker A loop in different nucleotide hydrolysis states. The protomer containing ATP or to-be-dissociated ADP (ADP’) are colored cyan and purple, respectively. Amino acids involved in polar interactions (depicted with yellow dotted lines) are shown as stick and labeled.