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. bond lengths and coordination number) of their binding sites are very well characterized. Alkaline earth cations such as calcium and magnesium are relatively easy to identify in electron density as the geometrical parameters (e.g.

While the stereochemistry of proteins and nucleic acids is well understood, there is no universal approach to describe the geometry of metal ion binding sites. In all the most popular programs used for macromolecular structure refinement, the restraints for metal-ligand interactions must be manually defined by the user. In addition to the stereochemical restraints for the macromolecule itself, it is essential to apply restraints to the metal ion-binding site (and subsequently interpret the electron density) taking into account the coordination properties of the cation. Therefore, the use of model restraints is a nearly universally applied technique in model building and structure refinement processes. For macromolecular structures, this ratio is usually low, due to the limited resolution of the data used to determine such structures. The ratio of the number of observed data to the number of parameters used in structure refinement depends on the data resolution and the number of atoms in a crystallographic asymmetric unit. This detailed analysis of the metal coordination architecture within proteins represents an important addition to the understanding of the biochemical functions of metalloproteins. 10% of the structures have a direct cation-ligand contact and the other 10% have a cation-ligand interaction bridged by an amino acid or ordered water molecules. Among 23,537 structures of proteins complexed with one or more small molecular ligands 20% contained one or more metal ions close to the ligand binding site that are likely to interact either directly or indirectly with the ligand. In the release dated Februof the Protein Data Bank (PDB), approximately 30% of structures contained metal ions. Moreover, in many cases metal ions are critical for crystal formation as the ions mediate crystal contacts between proteins. Metal ions are frequently observed in protein structures, and are often crucial for protein function, stability, or both. Correlation between data resolution and completeness of the metal coordination spheres is also found. Our analysis of cation B-factors versus average B-factors of atoms in the cation environment reveals substantial numbers of structures contain either an incorrect metal ion assignment or an unusual coordination pattern. For high resolution protein structures, the distribution of metal-protein or metal-water interaction distances agrees quite well with data from CSD, but the distribution is unrealistically wide for medium (2.0 – 2.5 Å) resolution data. The analysis compares data derived separately from high and medium resolution structures from the PDB with those from very high resolution small-molecule structures in the Cambridge Structural Database (CSD). Our approach may be used for fast identification of metal-binding structural motifs that cannot be identified on the basis of sequence similarity alone. By measuring the frequency of each amino acid in metal ion binding sites, the positive or negative preferences of each residue for each type of cation were identified. Analysis of metal-protein interaction distances, coordination numbers, B-factors (displacement parameters), and occupancies of metal binding sites in protein structures determined by X-ray crystallography and deposited in the PDB shows many unusual values and unexpected correlations.

Metal ion bonding methionine