Fig. 2: Photoisomerization leads to the formation of a metastable binding state. | Nature Communications

Fig. 2: Photoisomerization leads to the formation of a metastable binding state.

From: Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography

Fig. 2

A The two chemical structures of azo-CA4 show the wavelength-dependent conformational change between the cis (top) and trans (bottom) conformations. Central to the switch is the N=N azo bond that allows to switch azo-CA4 reversibly and with high efficiency between its high- and low-affinity stereoisomers, respectively. B Before laser-induced isomerization, cis-azo-CA4 (yellow sticks) is bound in the colchicine site located between the α (blue) and β (cyan) subunits close to the βT7 loop (green) of β-tubulin. Hydrophobic interactions (green lines) between tubulin residues and the A and B rings of cis-azo-CA4 as well as hydrophilic interactions (blue dashed lines) toward the ring substituents anchor the ligand within the colchicine site. C Within nanoseconds after illumination, trans-azo-CA4 (orange sticks) has relaxed into a metastable binding pose with an altered interaction network and reduced affinity. For clarity, only interacting residues are shown.

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