Carsten Krebs

Carsten Krebs

Main Content

  • Professor of Chemistry
  • Professor of Biochemistry and Molecular Biology
Office:
332 Chemistry Building
University Park, PA 16802
Email:
(814) 865-6089

Honors and Awards:

  1. SBIC Early Career Award, 2012
  2. Camille Dreyfus Teacher Scholar, 2006-2011
  3. Beckman Young Investigator, 2005-2008
  4. Pfizer Award in Enzyme Chemistry, 2008

Selected Publications:

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, ASAP.

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 synthaseJ. Am. Chem. Soc. 2016, 138, 8862-8874.

Rajakovich, L. J.; Nørgaard, H.; Warui, D. M.; Chang, W.-c.; Booker, S. J.; Krebs, C.; Bollinger, J. M., Jr.; Pandelia, M.-E. “Rapid Reduction of the Diferric-Peroxyhemiacetal Intermediate in Aldehyde-Deformylating Oxygenase by a Cyanobacterial Ferredoxin: Evidence for a Free-Radical MechanismJ. Am. Chem. Soc.  2015, 137, 11695-11709.

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 Beyondin “2-Oxoglutarate-Dependent Oxygenases” 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 AntibioticsScience 2014, 343, 1140-1144.

Krebs, C., Bollinger, J. M., Jr.; Booker, S. J. "Cyanobacterial alkane biosynthesis expands the functional and mechanistic repertoire of the "di-iron-carboxylate" proteins," Current Opinion Chem. Biol., 2011, 15, 291-303.

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.

Krebs, C.; Galonić Fujimori, D.; Barr, E. W.; Walsh, C. T.; Bollinger, J. M., Jr. "Non-heme Fe(IV)-Oxo Intermediates," Acc. Chem. Res., 2007, 40, 484-492.

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.

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.

Research Interests:

Biological

Spectroscopic and kinetic studies on the mechanisms of iron-containing enzymes

Inorganic

Mechanisms of metalloenzymes

Spectroscopy
Chemical Biology