Analysis of zinc binding sites in protein crystal structures

Abstract

The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.

Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation

“…The distance (2.17 Å) and angle (107.7°) between the Zn 2 þ and coordinating atom NE2 of histidine residues (Fig. 4a) were very close to those obtained from the analysis of 111 crystal structures 18 . The zinc-bridge model of zfP2X4 V291H/T214H based on the open crystal structure also produced reasonable values for the bond angle (110.2°) and bond lengths (2.14 Å; Supplementary Fig.…”

Generation of an activating Zn 2+ switch in the dopamine transporter: Mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle

“…Both the highly efficient targeting of Y335A to the cell surface and the ability of Zn 2ϩ to rescue transporter function with a potency similar to that observed for inhibition of the WT support that the overall structure is preserved in Y335A. Because of the very strict structural requirements for binding of the small Zn 2ϩ ion (25), even a minor structural change would be expected to be accompanied by reduced Zn 2ϩ affinity. The increases in apparent affinities for substrates in Y335A and the only slight change in apparent GBR-12,909 binding affinity support furthermore that the mutant transporter is in a functionally relevant conformation.…”

Structural Basis for Ni2+Transport and Assembly of the Urease Active Site by the Metallochaperone UreE from Bacillus pasteurii

“…1, C and D). Asn-98 O␦ forms an H-bond with His-100 N␦, further stabilizing the His-100 N⑀-Zn 2ϩ bond through a well conserved 'elecHis-Zn' motif (35). The BpUreE-Zn 2ϩ interaction, although not indispensable for the formation of the dimer 1 , supposedly further contributes to its stability.…”