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![[Figure 2]](ba5290fig2mag.jpg)
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Figure 2
Multitemperature multiconformer X-ray crystallography (MMX) for predicting allostery in protein structures. (a) MMX provides a way to infer how local regions of a protein structure mechanically couple to each other to facilitate allostery, as illustrated here schematically for a dynamic enzyme. At low temperature (e.g. 100 K), the active-site loop (top) and several residues linking the active site to a distal allosteric site (middle to bottom right) adopt a particular alternative conformation (blue) with higher probability or occupancy (thicker lines). As the temperature is increased (e.g. to >200 K), all of these regions concertedly shift their conformational ensemble to include increased populations of a different alternative conformation (red). This coupled behavior does not definitively prove, but is consistent with, the hypothesis that these regions are energetically coupled to each other and thereby form part of an interdependent allosteric network. By contrast, a different residue (bottom left) remains in a single conformation (purple) that is independent of temperature and thus is unresponsive to the other allosterically linked regions. The bottom-right binding site is therefore more likely to be capable of allosteric signaling to the active site than is the bottom-left binding site. (b) A molecular perturbation such as a small molecule (green) can test the hypothesis that different parts of the allosteric network are energetically coupled and that biasing the conformation of one part of the network biases the conformations of other parts. Artificial small molecules may compete with natural protein–protein interactions that play regulatory roles in cells (cyan). In addition, mutations (orange) may interfere with the energetic coupling between residues within the network. Thus, these other types of perturbations may equally well be used to interrogate allosteric networks that are predicted using MMX-based approaches. |
![[Figure 2]](ba5290fig2.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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