Carsten Krebs (he, him, his)
Professional Appointments
Professor of Chemistry
Professor of Biochemistry and Molecular Biology
Office
332 Chemistry Building
University Park, PA 16802
Email: cdk10@psu.edu
(814) 865-6089
Websites
Honors and Awards
Elected Fellow of the American Association for the Advancement of Science, 2019
SBIC Early Career Award, 2012
Pfizer Award in Enzyme Chemistry, 2008
Kavli Fellow of the National Academy of Sciences, 2007
Camille Dreyfus Teacher Scholar, 2006-2011
Beckman Young Investigator, 2005-2008
Information
Bioinorganic Chemistry - spectroscopic and kinetic studies on the mechanisms of iron-containing enzymes
Enzymes that contain the transition metal iron in their active sites exhibit great structural and functional diversity and play important roles in almost every aspect of life. The goal of our interdisciplinary research program is to combine biochemical, kinetic, and spectroscopic methods to study Fe-containing enzymes. The main technique used in our laboratory is 57Fe-Mössbauer spectroscopy. This technique provides information about oxidation state, spin state, coordination environment, and nuclearity of all chemically distinct iron species contained in a sample. In addition, it is possible to quantify all iron species. We combine this method with the rapid freeze quench (RFQ) method, and this allows us to monitor changes occuring at an iron site during a biochemical reaction. These studies (in conjunction with other techniques, such as stopped-flow absorption or RFQ EPR) provide detailed insight into the reaction mechanisms of iron-containing proteins.
Non-heme enzymes
Our main focus in this area involves enzymes that utilize a mononuclear or dinuclear non-heme-iron cofactor to activate dioxygen (or a partially reduced form thereof) to create potent reaction intermediates capable of performing difficult oxidation reactions. The Bollinger/Krebs joint group focuses on studying these reactions with a combination of kinetic, analytical, and various complementary spectroscopic methods by trapping and characterizing reaction intermediates.
Iron-sulfur cluster enzymes
Our main focus in this area is the study of the ‘Radical-SAM’ enzymes. These enzymes utilize a reduced [4Fe-4S] cluster to cleave S-adenosylmethionine (SAM) to methionine and a 5’-deoxyadenosylradical (5’-dAdo·) intermediate. The 5’-dAdo· is then used for various purposes. We study several "Radical SAM" enzymes (in most cases in collaboration with Squire Booker's group) by using 57Fe-Mössbauer spectroscopy.
Selected Publications
Rajakovich, L. J.; Zhang, B.; McBride, M. J.; Boal, A. K.; Krebs, C.; Bollinger, J. M., Jr. "Emerging Functional Diversity among Non-Heme Diiron Oxidases and Oxygenases" in "Comprehensive Natural Products III: Chemistry and Biology" ed. Liu, H.-w. and Begley, T. P., Elsevier, Amsterdam, 2020, x-x.
Zhang, B.; Arcinas, A. J.; Radle, M. I.; Silakov, A.; Booker, S. J.; Krebs, C. “The First Step in Catalysis of the Radical S-Adenosylmethionine Methylthiotransferase MiaB Yields an Intermediate with a [3Fe-4S]0-like Auxiliary Cluster” J. Am. Chem. Soc. 2020, 142, 1911-1924.
Dunham, N. P.; Del Río Pantoja, J. M.; Zhang, B.; Rajakovich, L. J.; Allen, B. D.; Krebs, C.; Boal, A. K.; Bollinger, J. M., Jr. “Hydrogen Donation but not Abstraction by a Tyrosine (Y68) During Endoperoxide Installation by Verruculogen Synthase (FtmOx1)” J. Am. Chem. Soc. 2019, 141, 9964-9979.
Blaesi, E. J.; Palowitch, G. M.; Hu, K.; Kim, A. J.; Rose, H. R.; Alapati, R.; Lougee, M. G.; Kim, H. J.; Taguchi, A. T.; Tan, K. O.; Laremore, T. N.; Griffin, R. G.; Krebs, C.; Matthews, M. L.; Silakov, A.; Bollinger, J. M., Jr.; Allen, B. D.; Boal, A. K. “Metal-Free Class Ie Ribonucleotide Reductase from Pathogens Initiates Catalysis with a Tyrosine-Derived Dihydroxyphenylalanine Radical” Proc. Natl. Acad. Sci., USA, 2018, 115, 10022-10027.
Dunham, N. P.; Chang, W.-c.; Mitchell, A. J.; Martinie, R. J.; Zhang, B.; Bergman, J. A.; Rajakovich, L. J.; Wang, B.; Silakov, A.; Krebs, C.; Boal, A. K.; Bollinger, J. M., Jr. “Two Distinct Mechanisms for C-C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of alpha-Heteroatom Assistance” J. Am. Chem. Soc. 2018, 140, 7116–7126.
Pan, J.; Bhardwaj, M.; Zhang, B.; Chang, W.-c.; Schardl, C. L.; Krebs C.; Grossman, R. B.; Bollinger, J. M., Jr. “Installation of the Ether Bridge of Lolines by the Iron- and 2-Oxoglutarate-Dependent Oxygenase, LolO: Regio- and Stereochemistry of Sequential Hydroxylation and Oxacyclization Reactions” Biochemistry 2018, 57, 2074-2083.
Kenney, G. E.; Dassama, L. M. K.; Pandelia, M.-E.; Gizzi, A. S.; Martinie, R. J.; Gao, P.; DeHart, C. J.; Schachner, L. F.; Skinner, O. S.; Ro, S. Y.; Zhu, X.; Sadek, M.; Thomas, P. M.; Almo, S. C.; Bollinger, J. M., Jr.; Krebs, C.; Kelleher, N. L.; Rosenzweig, A. C. “The Biosynthesis of Methanobactin” Science 2018, 359, 1411-1416.
Martinie, R. J.; Pollock, C. J.; Matthews, M. L.; Bollinger, J. M., Jr.; Krebs, C.; Silakov, A. “Vanadyl as a Stable Structural Mimic of Reactive Ferryl Intermediates in Mononuclear Nonheme-Iron Enzymes” Inorg. Chem. 2017, 56, 13382–13389.
Mitchell, A. J.; Dunham, N. P.; Martinie, R. J.; Bergman, J. A.; Pollock, C. J.; Hu, K.; Allen, B. D.; Chang, W.-c.; Silakov, A.; Bollinger, J. M., Jr.; Krebs, C.; Boal, A. K. “Visualizing the Reaction Cycle in an Iron(II)- and 2-(Oxo)-glutarate-Dependent Hydroxylase” J. Am. Chem. Soc. 2017, 139, 13830–13836.
Tamanaha, E.; Zhang, B.; Guo, Y.; Chang, W.-c.; Barr, E. W.; Xing, G.; St.Clair, J.; Ye, S.; Neese, F.; Bollinger, J. M., Jr.; Krebs, C. “Spectroscopic evidence for the two C-H-cleaving intermediates of Aspergillus nidulans isopenicillin N synthase” J. Am. Chem. Soc. 2016, 138, 8862-8874.
Bollinger, J. M., Jr.; Chang, W.-c.; Matthews, M. L.; Martinie, R. J.; Boal, A. K.; Krebs, C. “Mechanisms of 2-Oxoglutarate-Dependent Oxygenases: The Hydroxylation Paradigm and Beyond” in “2-Oxoglutarate-Dependent Oxygenases” ed. Hausinger, R. P. and Schofield, C. J.; The Royal Society of Chemistry, London, 2015, 95-122.
Chang, W.-c.; Guo, Y.; Wang, C.; Butch. S. E.; Rosenzweig, A. C.; Boal, A. K.; Krebs, C.; Bollinger, J. M., Jr. “Mechanism of the C5 Stereoinversion Reaction in the Biosynthesis of Carbapenem Antibiotics” Science 2014, 343, 1140-1144.
van der Donk, W. A.; Krebs, C.; Bollinger, J. M., Jr. "Substrate activation by iron superoxo intermediates," Current Opinion Struct. Biol., 2010, 20, 673–683.
Jiang, W.; Yun, D.; Saleh, L.; Barr, E. W.; Xing, G.; Hoffart, L. M.; Maslak, M.-A.; Krebs, C.; Bollinger, J. M., Jr. "A Stable Manganese(IV)/Iron(III) Cofactor Initiates Substrate Radical Production in Chlamydia trachomatis Ribonucleotide Reductase," Science, 2007, 316, 1188-1191.
Price, J. C.; Barr, E. W.; Tirupati, B.; Bollinger, J. M., Jr.; Krebs, C. "The First Direct Characterization of a High-Valent Iron Intermediate in the Reaction of an a-Ketoglutarate-Dependent Dioxygenase: A High-Spin Fe(IV) Complex in Taurine/a-Ketoglutarate Dioxygenase (TauD) from Escherichia coli," Biochemistry 2003, 42, 7497-7508.