= Solution
The three resistant substitutions map near one another in the folded <actin monomer>, near the <protein binding site> for the <nucleotide>. \b[This cluster identifies a candidate region involved in drug recognition or in the conformational response to binding.] Neighbouring residues in three-dimensional structure can help form a pocket even when they are not adjacent in the <protein primary structure>. Reduced drug binding at this region would connect the structural map to the resistant phenotype.
The map does not show a bound ToxB molecule. Substitutions could act indirectly by changing folding, <nucleotide> exchange or the assembly-competent conformation. Proximity to <ATP> does not prove competition for the ATP-binding site, and the mutant's abnormal baseline <actin polymerization> makes an allosteric explanation particularly relevant. Direct binding measurements on comparably folded wild-type and mutant <actin monomers>, together with nucleotide-binding controls and a ligand-bound structure, would distinguish these models. The allele/residue labels are interpreted as defined in this paper; no identification of their original experimental sequence substitutions is required.
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