Novel calcium recognition constructions in proteins: Calcium blade and EF-hand zone

Structural characterization of a prolyl aminodipeptidase (PepX) from Lactobacillus helveticus

“…The sixth coordination position is occupied by a water molecule that is also within hydrogen-bonding distance of the second O atom in the side chain of Asp198 (2.0 Å ) and the backbone carbonyl of Ser201 (2.3 Å ). This calcium-blade zone most closely resembles those identified in the seven-and eight-stranded -propeller folds of integrin -IIb (PDB entry 3t3p) and rhamnogalacturonan lyase (PDB entry 2zux) (Denesyuk et al, 2017;Zhu et al, 2012;Ochiai et al, 2009). To our knowledge, this is the first calcium-binding protein from the SCOP superfamily and with the /-hydrolase fold (SCOPe c.69 and c.69.1) that contains a calciumblade zone sequence and a calcium-binding blade-like site, increasing the number of identified distinct folds containing this motif from 12 to 13 (Denesyuk et al, 2017).…”

“…identified several examples of calcium-binding motifs across many different fold families all containing the DX(DN)XDG consensus sequence in a strand-loop-strand configuration, of which several occurred in -propeller proteins (Rigden et al, 2011;Rigden & Galperin, 2004). Denesyuk et al (2017) later defined a structural motif called the calcium-blade zone which describes the necessary interactions between the motif and the calcium ion beyond the three aspartic acid residues of the consensus sequence and identified how a calcium-blade zone differs from an EF-hand zone even though they may both contain the DX(DN)XDG consensus sequence.…”

Elucidating the Role of a Calcium-Binding Loop in an x-Prolyl Aminodipeptidase from Lb. helveticus

“…helveticus PepX calcium-binding site most closely resembles a structural motif proposed by Denesyuk et al called a calcium-binding blade-like site, in which the DxDxDG sequence is embedded within a 10 amino acid structural motif that forms a closed loop between secondary structural elements and that contains the consensus sequence xDx­[DN]­xDGxxD (LDTDHDGKSD in the case of Lb. helveticus PepX) . Tetragonal bipyramid coordination is achieved by aspartates at positions 2, 4, 6, and 10 which form coordinate bonds while a backbone carbonyl at position 8 also coordinates with the ion, and the sixth position is occupied by either water or an amino acid distant from the loop.…”

“…In canonical EF hands, the structural motif is found in a loop between two α-helices and consists of 12 semiconserved residues in positions 1, 3, 5, 7, 9, and 12 which are involved in coordinating the calcium along with a seventh position which is typically occupied by water to form a pentagonal bipyramid. 18,22,23 24 Tetragonal bipyramid coordination is achieved by aspartates at positions 2, 4, 6, and 10 which form coordinate bonds while a backbone carbonyl at position 8 also coordinates with the ion, and the sixth position is occupied by either water or an amino acid distant from the loop.…”

“…helveticus PepX). 24 Tetragonal bipyramid coordination is achieved by aspartates at positions 2, 4, 6, and 10 which form coordinate bonds while a backbone carbonyl at position 8 also coordinates with the ion, and the sixth position is occupied by either water or an amino acid distant from the loop.…”