Tungsten and Molybdenum Oxotransferases

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9808857 Johnson Mononuclear molybdenum or tungsten centers coordinated by the dithiolene units of one or two special pterin derivatives termed molybdopterin, terminal oxo/sulfido groups and/or protein side chains (serine, cysteine or selenocysteine) constitute the active sites of more than 30 distinct classes of oxotransferase enzymes involving formal oxygen atom transfer to or from water. The ubiquitous molybdoenzymes are involved in the metabolism of carbon, nitrogen and sulfur catalyzing a diverse range reactions spanning more than 800 mV in redox potential, whereas the tungstoenzymes are largely confined to thermophilic anaerobes in which they catalyze low potential conversions at the level of carboxylic acids and aldehydes. The objective of this research is to explore the structural and mechanistic diversity in this class of enzymes with particular emphasis on the role of the molybdopterin and terminal oxo ligands and the factors dictating the choice of tungsten or molybdenum. The approach is spectroscopic and exploits recent successes in using resonance Raman to probe the active site structures and catalytic mechanism via oxygen and sulfur isotopic labeling experiments and the combination of variable temperature magnetic circular dichroism and EPR to investigate ground and excited state electronic structure. Detailed understanding of the catalytic mechanisms of metallo-enzymes at the molecular level will ultimately lead to improved enzymes and catalysts for important biological and industrial applications. In addition to the biotechnological implications, this class of enzymes offer a unique opportunity to explore how a novel type of metalloenzyme active site has evolved via changes in the metal and ligand environment in response to evolutionary terrestrial changes and the need to catalyze a wider range of oxotransferase reactions.