High-pressure macromolecular crystallography as a tool for studying protein flexibility

Lieske, J.; Saouane, S.; Reinke, P.Y.A.; Falke, S.; Ewert, W.; Meyer, J.; Pakendorf, T.; Burkhardt, A.; Crosas, E.; Hakanpää, J.; Stachnik, K.; Sieg, J.; Rarey, M.; Aßmann, M.; Zaun, H.; Kuballa, J.; Selikhanov, G.K.; Gabdulkhakov, A.G.; Chapman, H.N.; Günther, S.; Meents, A.

doi:10.1107/S2052252526008468

Figure 5
Domain movements in kinases. Comparison of (a) the pressure-induced domain movement of DRAK2 (by 0.8°) and (b) the domain movement observed upon ATP binding to the mammalian cAMP-dependent protein kinase A (PKA) (by 15.9°). Central cleft closure is observed upon ATP binding to PKA and – to a much smaller extent – upon pressure perturbation in DRAK2. The structures at atmospheric pressure and the corresponding nucleotide-free form are shown in green, whereas the 110 MPa structure and the ATP-bound state are colored pink. The structures are superimposed on their N-lobes (right-hand domains) and the C-lobes of the reference states are highlighted as light-gray surfaces. The rotation axes of the hinge movements as determined via the DynDom server (Girdlestone & Hayward, 2016

) are represented as blue rods. PKA structures 1cmk (free form) and 1atp (ATP-bound form) (Zheng et al., 1993

) were taken from the Protein Data Bank.

IUCrJ

Volume 13| Part 6| November 2026|

ISSN: 2052-2525

https://doi.org/10.1107/S2052252526008468

BIOLOGY | MEDICINE

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