Geometry of metal–ligand interactions in proteins

Abstract

The geometry of metal-ligand interactions in proteins is examined and compared with information for small-molecule complexes from the Cambridge Structural Database (CSD). The paper deals with the metals Ca, Mg, Mn, Fe, Cu, Zn and with metal-donor atom distances, coordination numbers and extent of distortion from ideal geometry (octahedral, tetrahedral etc.). It assesses the agreement between geometry found in all metalloprotein structures in the Protein Data Bank (PDB) determined at resolution < or = 1.6 A with that predicted from the CSD for ligands which are analogues of amino-acid side chains in proteins [Harding (1999), Acta Cryst. D55, 1432-1443; Harding (2000), Acta Cryst. D56, 857-867]. The agreement is reasonably good for these structures but poorer for many determined at lower resolution (examined to 2.8 A resolution). For metal-donor distances, the predictions from the CSD, with minor adjustments, provide good targets either for validation or for restraints in refinement of structures where only poorer resolution data is available. These target distances are tabulated and the use of restraints is recommended. Validation of angles or the use in refinement of restraints on angles at the metal atom is more difficult because of the inherent flexibility of these angles. A much simplified set of parameters for angle restraints with quite large standard deviations is provided. (Despite the flexibility of the angles, acceptable and preferred coordination numbers and shapes are well established and a summary table is provided.) An unusual and perhaps biochemically important feature of Zn coordination with carboxylate seen in the CSD examples is also clearly present in metalloprotein structures. With metals like Ca, carboxylate coordination is monodentate or bidentate (two M-O bonds of nearly equal length). In Zn carboxylates a continuous range between monodentate and bidentate coordination is found, with one Zn-O bond of normal length and another of any length between this and a van der Waals contact.

An approach to crystallizing proteins by metal‐mediated synthetic symmetrization

“…Specifically, we predicted the metal site within these assemblies to take on a tetrahedral or octahedral coordination, in which the mutated histidines or cysteines among the molecules participate in the metal coordination. Such coordination geometries are commonly found in proteins 33,54 and have been engineered previously. [37][38][39][40][41][42] On the basis of the crystal structures of T4L and MBP in each protein, we chose three pairs of solvent-accessible residues that are located close to the ends of helices (Fig.…”

“…For T4L, we created two double-histidine mutants, T4L 76H/80H and T4L 61H/65H , and one quadruple-histidine mutant, T4L 61H/65H/76H/80H , chosen to emulate the engineering design by Tezcan et al 33 in which four histidine mutations are introduced as two pairs of proximal residues in a long helix. Crystallization of these mutants with the various metals resulted in eight crystal structures (Table I), which represent six distinct crystal forms; in some mutants, nickel and copper produced similar metal-binding sites and crystal packing arrangements.…”

“…[33][34][35] For example, in the high-resolution crystal structure of truncated alphaA crystallin, 36 a zincbinding motif is formed by three chains, and zinc promotes protein oligomerization and crystallization. The compound tetrathiomolybdate, used in the treatment of copper metabolism disorders, reacts with the copper binding metallochaperone, Atx1, forming a stable complex.…”

Data mining of metal ion environments present in protein structures

“…Alkaline earth cations such as calcium and magnesium are relatively easy to identify in electron density as the geometrical parameters (e.g. bond lengths and coordination number) of their binding sites are very well characterized [5][6][7][8]. Alkali metal ions such as sodium and potassium, however, are more difficult to identify because their coordination spheres are not as regular as those of alkaline earth metal ions [9].…”

“…Studies describing the geometry of metal ion-binding sites within proteins and in small molecule structures were recently extensively discussed in a series of papers by Harding [5][6][7][8][9]11]. Here, in contrast, our objective is to analyze the properties of metal ion binding sites in protein structures as a function of structure resolution and crystallographic methodology.…”