Bio-inorganic chemistry

Abstract

Abbreviations NO nitric oxide SOD superoxide dismutase Of the ninety or so nonradioactive elements in the Earth's crust up to thirty are thought to be essential for plant, animal and microbial life. Only eleven elements occur in all known organisms and plants: they are hydrogen, carbon, nitrogen, oxygen, sodium, potassium, calcium, magnesium potassium, sulfur and chlorine. In addition, a further ten elements and nonmetals are needed by most, and an additional eight are required by some, species only. The eighteen elements are vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, molybdenum, tungsten, boron, silicon, selenium, fluorine, iodine, arsenic, bromine and perhaps tin. In this volume we have selected accounts that describe the biological chemistry of some of these elements, namely calcium, vanadium, nickel, copper, zinc, molybdenum and tungsten. This choice is governed in part by the rapid progress in our understanding of their functions in biology. Other chapters focus on important cofactors that contain metal ions such as haem and iron-sulfur clusters, and on the functional significance of certain groups of enzymes. Our viewpoint, however, is almost invariably from that of the discipline of inorganic chemistry (that is, we explore the coordination chemistry employed by biology in its many subtle and unexpected forms). It has been estimated that over 50 % of all proteins will turn out to be metalloproteins. Hence the field is already so vast that it is not possible to cover it in a single volume. Recently, a number of excellent texts and reviews have appeared which will allow the reader to follow the field more comprehensively [1-6]. The activation of oxygen both by mononuclear and dinuclear nonhaem iron sites is described by Lange and Que (pp 159-172). The rapidly increasing number of crystal structures is revealing common structural motifs used widely in the mononuclear iron(II) enzymes in which a set of ligands, two histidine residues and one carboxylate group, form a triad on the face of an octahedron. The addition of further ligands, such as a thiolate in isopeni-cillin N-synthase or tyrosine in tyrosine hydroxylase, causes the iron(II) coordination sphere to bind oxygen and the enzymatic cycle to begin. In this way binding of oxygen is conditional upon substrate being in place before activation occurs. Unwanted reactions of iron(II) and dioxygen (O2) are thereby minimised and dangerous side effects avoided. The power of protein crystallography to reveal a complete reaction cycle in an enzyme is elegantly seen in the thirteen structures of the catechol dioxygenase by Ohlendorf and co-workers [7,8]. The field of dinuclear nonhaem iron enzymes is also moving rapidly with the identification of high valent iron intermediates of methane monooxygenase and ribonucleotide reductase being characterised by a combination of spectroscopic and extended X-ray absorption fine structure (EXAFS) methods. The value of synthetic models to allow such chemistry to be described at the level of molecular resolution is nowhere better seen. Although the area of iron-sulfur chemistry is, after hacmoprotein chemistry, one of the most long studied, there are recent important and exciting discoveries,which are described by Johnson (pp 173-181). These range from the characterisation of the electronic properties of mixed valence clusters, the discovery of highly reduced all ferrous clusters, to the emergence of new roles for iron-sulfur clusters in genc regulation and enzymology, The rcalisation that the bridging sulfido ions of the clusters may have a chemistry of biological relevance-including reactions with nitric oxide (NO), reactions with protons and in catalysis of disulfide reduction-is giving a fresh vigour to the subject. Bacterial nitrogen metabolism cycles nitrogen from the oxidation state of-3 (NH 3) to +5 (NO3-), in three distinct segments: NZ-~NH 3 (fixation), NH3-+NO3-, (nitrifica-tion) and NO3-~N2 (denitrification). Each one of seven steps employs a metalloenzymc involving molybdenum, vanadium, iron or copper. Some of the steps are carried out by more than one class of enzymes; for example, there are two classes of nitrate reductases and at least three nitrogenase proteins. In the denitrification path there arc distinct enzymes for assimilation of nitrogen and for dissimilation to yield energy. The complete set of this rich array of enzymes has now been cloned and purified. The progress made in obtaining structural details and mechanism is described in the article by Ferguson (pp 182-193). If the diversity brought about by species is added, the molecular complexities rapidly increase. The excitement generated by the resolution of the remarkable structure of nitrogenase itself is being maintained by solution of the structure of the protein-protein complexes of the iron-and molybdenum-containing nitrogenases,