Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations
Fig 8
Opening and closing of the substrate binding pocket and movement of helix 2 based on superpositioning of bound and unbound acetylase domains.
Sidechains of the putative induced fit glutamate and arginine residues in the closed form are shown as red and yellow sticks, respectively. CoA within half-bound homodimers is shown as cyan colored sticks. A. Node 42 CoA-bound, CoA-unbound and CoA-half-bound structures. When bound to CoA, helix-2 moves outward relative to the unbound homodimer. The sidechain of the 3dr8 arginine residues (open conformation) for the 3dr8 vs 3dr6 superposition is shown as light blue sticks (compare with Fig 7A). B. Node 35 hierarchy with color coding. C. Node 41 unbound monomeric structure superimposed over the node 42 CoA-bound homodimer. Note that the proposed induced-fit arginine residue is replaced by a tyrosine, which could also form both a hydrogen bond to the glutamate residue and a π- π stacking interaction with this tyrosine from the other homodimeric subunit. D. Node 39 superpositions showing that, unlike sequences assigned to the node 40 subtree, helix 2 does not appear to move outward upon binding to CoA. This may be due to differences between node 40 and node 36 pattern residues associated with this helix (see Fig 7D–7F).