Structure-Based Statistical Mechanical Model Accounts for the Causality and Energetics of Allosteric Communication
Fig 2
Two examples of the hetero-oligomeric allosteric proteins, the 12-mer Aspartate carbamoyltransferase ATCase (A) and 4-mer Anthranilate Synthase AnthS (B).
In (A) the averaged free energy Δgi(0 → 6xATP/CPT) profiles per monomer (red curves) are shown for the catalytic (PAL site) and regulatory (ATP-CTP site) chains with gray error bands. The positions of residues that belong to the allosteric and catalytic sites are marked with corresponding symbols. In the upper right panel the complex surface is colored according to the values of the conformational work per residue. The regulatory chains are strongly stabilized (red part of the Δg scale), whereas the chains that carry catalytic sites yield a significant increase of configurational work (blue part of the Δg scale) as a result of allosteric communication between sites. Catalytic (PAL) and regulatory (ATP-CTP) sites are shown in green and red, respectively. In (B) the averaged free energy Δgi(0 → 2xTRP) profiles are shown for chains 1–2 (BEZ and TRP site) and chains 3–4 (GLU site) of Anthranilate Synthase AnthS. Similarly to the ATCase allosteric sites, the restraining in chains 1–2 induces high configurational work in the chains 3–4 that contain catalytic sites. Here and in the following figures containing data on proteins the red curve in the chart shows allosteric free energy profiles, the grey error band reflects the range in the amount of work exerted per residue in each monomer, because of the structural differences between homologous monomers in the oligomeric structure. Surface representations are colored according to the conformational work exerted per residues in corresponding part of the protein (red—negative values of the conformational work, showing local stabilization; blue—positive values of the work, pointing to increase of the local dynamics). We also show representative structures with color-marked locations of the corresponding ligands.