Preface

In the late 1950s and early 1960s, evidence was accumulating that molybdenum was not simply present in the enzyme xanthine oxidase from cow's milk but that it was required for its activity and changed its oxidation state in the course of the reaction with substrate. In a tour-de-force isotopic substitution study reported in Nature in 1966, R.C. Bray and L.S. Meriwether demonstrated unequivocally that the EPR signals elicited by the enzyme upon treatment with xanthine arose from a molybdenum-containing active site. It is a happy coincidence but altogether fitting that this volume marks the 50th anniversary of this seminal work.

For many years, only five enzymes were recognized as possessing molybdenum in their active sites: nitrogenase from bacteria such as Klebsiella pneumoniae and Azotobacter vinelandii; xanthine oxidase from bovine milk (and other vertebrate sources); aldehyde oxidase from vertebrate as well as bacterial sources; the vertebrate sulfite oxidase; and the assimilatory nitrate reductase from plants (and algae and fungi). That began to change in the 1980s with the demonstration by K. V. Rajagopalan that an organic cofactor accompanied the molybdenum in the active sites of these enzymes (with the exception of nitrogenase), and with the contemporaneous discovery that tungsten was also found in the active sites of enzymes in certain bacteria.

There are now several dozen molybdenum- and tungsten-containing enzymes that have been crystallographically characterized, along with most of the enzymes responsible for the biosynthesis of the organic cofactor variously known as molybdopterin, tungstopterin and pyranopterin. The active site metal centres of these enzymes have proven to be fascinating and challenging targets for synthetic inorganic chemists, and both enzymes and synthetic models have proven fertile ground for the application of a range of physicochemical and spectroscopic methods probing their physical and electronic structures as well as their intrinsic reactivity. At present, well over 50 molybdenum- and tungsten-containing enzymes have been isolated and characterized, and these have been found to catalyze a broad range of oxidation-reduction reactions, and even reactions that (at least formally) do not involve oxidation–reduction of substrate. These enzymes are found in a wide range of metabolic pathways and play particularly prominent roles in the global cycling of nitrogen, sulfur and carbon. Many have vital roles in bacterial bioenergetics, catalyzing crucial energy-conserving reactions under a variety of growth conditions. Indeed, they seem to have been among the earliest enzyme systems to have arisen, as reflected in their near-universal distribution in the biosphere. Finally, genomics analyses have led to the identification of hundreds of genes encoding putative new proteins that are likely to possess one or another metal. These systems represent an enormous frontier of new enzymes that remains to be explored.

This title provides an up-to-date account of the state of our understanding of molybdenum and tungsten enzymes and is divided into three volumes, dealing with: (1) the enzymes themselves, along with pyranopterin cofactor biosynthesis and incorporation of the mature cofactor into apoprotein (Molybdenum and Tungsten Enzymes: Biochemistry), (2) inorganic complexes that model the structures and/or reactivity of the active sites of each major group of molybdenum and tungsten enzymes (Molybdenum and Tungsten Enzymes: Inorganic Chemistry) and (3) spectroscopic and related methods of physical chemistry (including computational work) that have been applied to both enzymes and model compounds (Molybdenum and Tungsten Enzymes: Physical Methods). Each volume is introduced by an overview chapter written by a leading expert in the field, followed by the individual chapters that detail specific topics associated with each volume. The intent of these overview chapters is to provide an overarching and unifying theme that places each of the three major subject areas in proper context.

We are deeply indebted to each of the contributors for their efforts, which lay out the current state of our understanding in each of the many subject areas considered. The coverage of these volumes is inevitably incomplete due to space constraints, however, and for this we apologize. However, the topics that are covered are presented to the reader in considerable detail; written in a style and spirit that will be fully accessible by current researchers in the field as well as those who wish to learn more about these fascinating metalloproteins. We sincerely hope that these volumes will underscore how rapid the progress has been over the past decade or so, and also how rapidly the field is expanding. The ultimate goal is to stimulate further research on molybdenum and tungsten enzymes, and especially to encourage new investigators to take up one or another aspect of these systems. It seems inevitable that many exciting new discoveries lie in wait.

Russ Hille

Carola Schulzke

Martin L. Kirk