English: The helix-loop-helix EF-hand Ca²⁺ binding motif. (A), Cartoon illustration of the canonical EF-hand Ca²⁺-binding motif. The EF-hand motif contains a 29-residue helix-loop-helix topology, much like the spread thumb and forefinger of the human hand. Ca²⁺ is coordinated by ligands within the 12-residue loop, including seven oxygen atoms from the sidechain carboxyl or hydroxyl groups (loop sequence positions 1, 3, 5, 12), a main chain carbonyl group (position 7), and a bridged water (via position 9). Residue at position 12 serves as a bidentate ligand. The Ca²⁺ binding pocket adopts a pentagonal bipyramidal geometry. n stands for hydrophobic residue. (B), HMM logo for the canonical EF hand motif (http://pfam.sanger.ac.uk/family?acc=PF00036). The conservation of amino acids at several positions makes it possible to predict EF-hand motifs from genomic sequences. (C), 3D structure of a typical canonical EF-hand motif from calmodulin (PDB code: 3cln). Ca2+ is chelated by ligands from a 12-residue loop. (D), 3D structure of an EF-hand-like motif from a soluble fragment of lytic transglycosylase B of Escherichia coli (PDB code: 1qut). This motif contains a 15-residue (instead of 12-residue) Ca²⁺-binding loop flanked by two helices.