Pterin containing molybdenum enzymes are found in all forms of life, they catalyze numerous reactions that provide vitality in life processes. At the catalytic heart of these enzymes resides a remarkable molecule called molybdopterin that harbors multiple redox active components, and binds molybdenum. In humans, absence of this cofactor due to genetic disposition results in severe physiological disorders including death. The long- term objective of our research program is to understand enzymatic function in order to improve the quality of human health and the environment. While over fifty years of continued research on molybdenum enzymes has made strides, there exist significant gaps in our understanding of the relationship between the structure and the function of molybdopterin enzymes. The specific goals of this research are: to examine what controls the substrate binding and catalytic efficiency in periplasmic nitrate reductase in pathogenic Campylobacter jejuni; to understand how redox states of the dithiolene can influence the spectroscopic properties and electronic description of the molybdenum center; and to develop synthetic strategies for preparing the complete molybdenum cofactor. The proposed research is noteworthy because it will help develop a significantly superior understanding of the chemical properties of a vital biomolecule that is a key component in many life processes. In addition, the proposed research also investigates an important enzyme from a pathogenic organism that infects nearly half a billion people yearly with an estimated cost of $8 billion dollars. The proposed research is related to public health because, a) in Campylobacter jejuni periplasmic nitrate reductase is potentially involved in pathogenicity, and the result generated from the proposed research may allow developing future therapeutics; b) developing the synthetic procedures for molybdenum cofactor may lead to therapy of the genetic disorder due to molybdenum cofactor deficiency; and c) new important knowledge will be generated about the structure-function of an important class of enzyme which in turn can help improve human health. Therefore, the proposed research is relevant to the NIH's mission as it pertains to the pursuit of fundamental knowledge regarding the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce the burdens of ailment.
Pterin containing molybdenum enzymes are important for human health, and this proposal addresses some of the basic questions about their structure and redox properties. We also investigate the periplasmic nitrate found in pathogenic bacteria catalyzes using biochemical approaches.
| Ratvasky, Stephen C; Mogesa, Benjamin; van Stipdonk, Michael J et al. (2016) A mixed valence zinc dithiolene system with spectator metal and reactor ligands. Polyhedron 114:370-377 |
| Yang, Jing; Mogesa, Benjamin; Basu, Partha et al. (2016) Large Ligand Folding Distortion in an Oxomolybdenum Donor-Acceptor Complex. Inorg Chem 55:785-93 |
| Mogesa, Benjamin; Perera, Eranda; Rhoda, Hannah M et al. (2015) Solution, Solid, and Gas Phase Studies on a Nickel Dithiolene System: Spectator Metal and Reactor Ligand. Inorg Chem 54:7703-16 |
| Basu, Partha; Burgmayer, Sharon J Nieter (2015) Recent developments in the study of molybdoenzyme models. J Biol Inorg Chem 20:373-83 |
| Sparacino-Watkins, Courtney; Stolz, John F; Basu, Partha (2014) Nitrate and periplasmic nitrate reductases. Chem Soc Rev 43:676-706 |
| Pimkov, Igor V; Peterson, Antoinette; Vaccarello, David N et al. (2014) A Regioselective Synthesis of the Dephospho DIthiolene Protected Molybdopterin. RSC Adv 4:19072-19076 |
| van Stipdonk, Michael J; Basu, Partha; Dille, Sara A et al. (2014) Infrared multiple photon dissociation spectroscopy of a gas-phase oxo-molybdenum complex with 1,2-dithiolene ligands. J Phys Chem A 118:5407-18 |
| Hille, Russ; Hall, James; Basu, Partha (2014) The mononuclear molybdenum enzymes. Chem Rev 114:3963-4038 |
| Pimkov, Igor V; Nigam, Archana; Venna, Kiran et al. (2013) Dithiolopyranthione Synthesis, Spectroscopy and an Unusual Reactivity with DDQ. J Heterocycl Chem 50:879-886 |
| Deibler, Kristine; Basu, Partha (2013) Continuing issues with Lead: Recent Advances in Detection. Eur J Inorg Chem 2013:1086-1096 |
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