Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

The Molybdenum Cofactor and Pyranopterin Mo Enzyme Catalysis (121638)

Martin Kirk 1
  1. The University of New Mexico, Albuquerque, NM, United States

Pyranopterin molybdenum enzymes possess a unique Mo-bound pyranopterin dithiolene (Mo-MPT = Moco) cofactor.1These critical enzymes are essential to human health and life processes, catalyzing important chemical transformations in the metabolic pathways of sulfur, nitrogen, and carbon compounds.2 New work from our laboratories has contributed to a greater understanding of DMSO reductase family enzyme catalysis,3 new types of molybdenum enzyme catalyzed chemical transformations that extend beyond simple oxygen atom transfer reactivity,4 and new roles for the pyranopterin dithiolene component of the Mo cofactor (Moco) in catalysis.5-7 Here, we will highlight our synthetic, structural, spectroscopic, computational, and molecular biology approaches to solving some of the most important problems in this exciting field.

  1. 1. Probst C., Yang J., Krausz J., Hercher T.W., Richers C.P., Spatzal T., Khadanand KC, Giles L.J., Rees D.C., Mendel R.R., Kirk M.L., Kruse T., Nature Chemistry, 2021, 13, 758-765.
  2. 2. Ingersol L.J., Kirk M.L., in Comprehensive Coordination Chemistry III, eds. E. C. Constable, G. Parkin and L. Que Jr, Elsevier, Oxford, 2021, Ch. 8.31, pp. 790-811.
  3. 3. Yang, J., Mintmier, B., KC, K., Metzger, M.; Radhakrishnan, M., McGarry, J., Wilcoxen, J., Basu, P.; Kirk , M.L., 2024. Inorganic Chemistry, 63, 29, 13191-13196.
  4. 4. Struwe, M., Yang, J., Kolanji, K., Mengell, J., Scheidig, A., Clement, B., Kirk, M. L., 2024. Inorganic Chemistry, 63, 41, 19063–19073.
  5. 5. Gates C., Varnum H., Getty C., Loui N., Chen J., Kirk M.L., Yang J., Nieter Burgmayer S.J., Inorg. Chem., 2022, 61, 13728-13742.
  6. 6. Burgmayer S.J.N., Kirk M.L., in Metallocofactors that Activate Small Molecules: With Focus on Bioinorganic Chemistry, ed. M. W. Ribbe, Springer International Publishing, Cham, 2019, vol. 179, pp. 101-151.
  7. 7. Burgmayer, S., Kirk, M.L., Advancing our Understanding of Pyranopterin-Dithiolene Contributions to Moco Enzyme Catalysis, Molecules, 2023 28, 22. 7456.