IUCr journals

Anomalous dispersion analysis of inhibitor flexibility: a case study of the kinase inhibitor H-89

Acta Cryst. (2012). F68, 873-877 (http://doi.org/h94)

[Density map] Anomalous difference density map (4 σ) from the bromine signal shows two binding positions for the atom, with consequences for the modelling of a linker segment.

The anomalous dispersion signal from bromine was used to identify two binding geometries for the inhibitor H-89 bound to protein kinase A (PKA). Inhibitors often bind to proteins flexibly, with a range of binding geometries, but limited data resolution (or automated structure solution) may hinder their explicit inclusion into a structural model. Instead, flexibility is implicitly modelled with high temperature factors, implying more broadly unstructured binding throughout the volume in question. The serendipitous presence of an anomalous scatterer in the inhibitor enables more accurate modelling.

A. Pflug, K. A. Johnson and R. A. Engh