Lubom õr Rul õ sek *, Ji r õ Vondr a sek
m. 2, 16610 Prague 6, Czech Republic Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo na Received 5 January 1998; received in revised form 18 June 1998; accepted 7 July 1998
1. Introduction Interactions of metals with biomolecules belong to one of the most studied ®elds in inorganic biochemistry. The areas of application of new knowledge or information may range from medicinal chemistry [1] through ``classical'' organometallic chemistry to environment protection (metal-binding biomass [2]). The role of metal ions in the structure and function of proteins, nucleic acids, and peptide hormones is fundamental, yet often unknown at the molecular level. The hypotheses about principles governing selectivity and speci®city of macromolecules for a given metal are often based on semiempirical and qualitative theories, such as the HSAB (hard and soft acids and bases) principle of Parr and Pearson, [3,4] and Irving±Williams series of stability constants for divalent ions [5,6]. A plethora of experimental and theoretical material about the interactions of metals with biological macromolecules is compiled in several excellent reviews [7±10]. Besides, there are papers dealing with structural aspects of metal binding in biomolecules [11,12]. We are not
Journal of Inorganic Biochemistry 71 (1998) 115±127
Coordination geometries of selected transition metal ions (Co2, Ni2, Cu2 , Zn2, Cd2 , and Hg2) in metalloproteins
0162-0134/98/$ ± see front matter Ó 1998 Elsevier Science Inc. All rights reserved. PII: S 0 1 6 2 - 0 1 3 4 ( 9 8 ) 1 0 0 4 2 - 9
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 L. Rulõ sek, J. Vondr a sek / J. Inorg. Biochem. 71 (1998) 115±127
The transition metal elements analyzed here were selected because of two reasons. First, their metalloprotein complexes belong to the most abundant. Second, these metals are the major pollutants of the environment. Cadmium and mercury are highly toxic heavy metals. Nickel, cobalt, and copper, as representatives of the ®rst-row transition metals, are undesirable elements in the environment as well. The same holds true for zinc (biogenic element) which is toxic in higher concentrations. The development of methods for selective binding of these metals may ultimately lead to their successful removal from the environment (see for example Ref. [2]). The molecular design of such speci®c sites should necessarily start with the type of structural information we are trying to provide here. We presume that it cannot be obtained by a purely theoretical approach, represented by ab initio calculations, but can be revealed by careful analysis of the experimental structures.
Abstract In order to determine preferred coordination geometries of six divalent cations (Co2 , Ni2 , Cu2 , Zn2 , Cd2 , and Hg2 ), two sources of experimental data were exploited: Protein Data Bank and Cambridge Structural Database. Metal-binding sites of approximately 100 metalloproteins and 3000 smaller transition metal complexes were analyzed and classi®ed. The correlation between the geometries of small-molecule crystal structures and the metal-binding sites in metalloproteins was investigated. The abundance of amino acid residues participating in coordination metal-protein bonds of metalloproteins was evaluated. From the performed analysis it follows that the octahedral arrangement is preferred by Co2 and Ni2 , tetrahedral by Zn2 , square planar by Cu2 , and linear by Hg2 . Cadmium (II) cation tends to bind in both tetrahedral and octahedral arrangements and single coordination geometry cannot be unambiguously ascribed to it. Ó 1998 Elsevier Science Inc. All rights reserved. Keywords: Metal-binding site; Coordination geometry; Metalloproteins; Metal-binding residue
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Corresponding author. E-mail: lubos@uochb.cas.cz
aware of any recent study summarizing all publicly available structural information about the geometries of transition metal binding sites. Therefore, we have carried out a comprehensive analysis of the known structures of metallopபைடு நூலகம்oteins containing selected transition metals to ®nd the correlation between the small-molecule crystal structures of speci®ed metals and their coordination in metalloproteins. Our work is intended to draw nearer the facts known from basic inorganic chemistry textbooks [13] and the facts known about the structure and function of metalloproteins. We endeavor to investigate in a purely empirical and statistical way if the principles and mechanisms determining the structures of small-molecule complexes (such as ligand-®eld stabilization energy and charge transfer from ligands to metal) remain unchanged when describing the complex metal-binding sites in metalloproteins. This can be proved by the degree of correlation found between the distribution of coordination geometries among small-molecule complexes and metalloproteins. The other questions are whether single coordination geometry could be identi®ed as preferred for a particular metal and to what extent does a given metal prefer coordination sites with this geometry.