Integrating structure-based machine learning and co-evolution to investigate specificity in plant sesquiterpene synthases
Fig 4
A. Tobacco epi-aristolochene synthase (TEAS) secondary structure with distal cation-specific co-evolutionary contacts (green arcs), motif residues (purple), and cation-specific residues (colored by region). Helix naming as in Starks et al. [26] B. Sequence-pair conservation of four cation-specific contacts discussed in the text, across farnesyl and nerolidyl cation-specific STSs, and all putative terpene synthases. The height of a pair of letters represents the frequency of the pair appearing in those two positions, with ‘X’ representing gaps. C. Diagrams indicating the proximity of residues labeled B in Fig 3B, as well as the residues that they co-evolve with, to substrate analogs trifluorofarnesyl diphosphate (FFF) co-crystallized with TEAS (left) and farnesyl thiodiphosphate (FPS) co-crystallized with Abies grandis α-bisabolene synthase (AgBIS) (right). Carbon atoms are numbered (white boxes) as in the FFF subtrate analog moeity in PDB ID 5EAU. The closest distance (in Å) between each residue’s β-carbon and a substrate atom is labeled in gray. Two co-evolving contacts (labeled 1 and 2 in A) are colored in green.