Structure of calmodulin refined at 2.2 Å resolution

The crystal structure of mammalian calmodulin has been refined at 2.2 Å (1 Å = 0.1 nm) resolution using a restrained least-squares method. The final crystallographic R-factor, based on 6685 reflections in the range 2.2 Å ≤ d ≤ 5.0 Å with intensities exceeding 2.5 σ, is 0.175. Bond lengths and bond angles in the molecule have root-mean-square deviations from ideal values of 0.016 Å and 1.7 °, respectively. The refined model includes residues 5 to 147, four Ca 2+ and 69 water molecules per molecule of calmodulin. The electron density for residues 1 to 4 and 148 is poorly defined, and they are not included in the model. The molecule is shaped somewhat like a dumbbell, with an overall length of 65 Å; the two lobes are connected by a seven-turn α-helix. Prominent secondary structural features include seven α-helices, four Ca 2+-binding loops, and two short, double-stranded antiparallel beta-sheets between pairs of adjacent Ca 2+-binding loops. The four Ca 2+-binding domains in calmodulin have a typical EF hand conformation (helix-loop-helix) and are similar to those described in other Ca 2+-binding proteins. The X-ray structure determination of calmodulin shows a large hydrophobic cleft in each half of the molecule. These hydrophobic regions probably represent the sites of interaction with many of the pharmacological agents known to bind to calmodulin.