Carsten D. Krebs

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

Selected Publications:

Dassama, L. M. K.; Yosca, T. H.; Conner, D. A.; Lee, M.; Blanc, B.; Streit, B. R.; Green, M. T.; DuBois, J. L.; Krebs, C.*, Bollinger, J. M., Jr.* "O2-evolving Chlorite Dismutase as a Tool to Study O2-Utilizing Enzymes," Biochemistry, 2012, DOI: 10.1021/bi201906x

Dassama, L. M. K.; Boal, A. K., Krebs, C.*; Rosenzweig, A. C.; Bollinger, J. M., Jr.*  "Evidence that the β Subunit of Chlamydia trachomatis Ribo-nucleotide Reductase is Active with the Manganese Ion of its Manganese(IV)/Iron(III) Cofactor in Site 1," J. Am. Chem. Soc., 2012, 134, 2520-2523.

Grove, T. L.; Radle, M. I.; Krebs, C.*; Booker, S. J.* "Cfr and RlmN Each Contain Only One [4Fe–4S] Cluster, which Is Required Both for Formation of the Protein Methylcysteinyl Intermediate and Generation of the 5’-Deoxyadenosyl 5’-Radical," J. Am. Chem. Soc., 2011, 133, 19586-19589.

Grove, T. L.; Benner, J. S.; Radle, M. I.; Ahlum, J. H.; Landgraf, B. J.; Krebs, C.; Booker, S. J.*  "A Radically Different Mechanism for S-adenosylmethionine-dependent Methyltransferases Exhibited by the Antibiotic Resistance Protein Cfr and its Homologue RlmN," Science 2011, 332, 604-607.

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.

Li, N.; Nørgaard, H.; Warui, D. M.; Booker, S. J.; Krebs, C.; Bollinger, J. M., Jr.  "Conversion of Fatty Aldehydes to Alka(e)nes and Formate by a Cyanobacterial Aldehyde Decarbonylase: Cryptic Redox by an Unusual Dimetal Oxygenase," J. Am. Chem. Soc., 2011, 133, 6158-6161.

Warui, D. M.; Li, N.; Nørgaard, H.; Krebs, C.*, Bollinger, J. M., Jr.*; Booker, S. J.*  "Detection of formate, rather than carbon monoxide, as the stoichiometric co-product in conversion of fatty aldehydes to alkanes by a cyanobacterial aldehyde decarbonylase," J. Am. Chem. Soc., 2011, 133, 3316-3319.

Panay, A. J.; Lee, M.; Krebs C.; Bollinger, J. M., Jr.; Fitzpatrick, P. F. *  "Evidence for a High Spin Fe(IV) Species in the Catalytic Cycle of a Bacterial Phenylalanine Hydroxylase," Biochemistry, 2011, 50, 1928-1933.

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.

Li, N.; Korneeva Korboukh, V.; Krebs, C.*; Bollinger, J. M., Jr.*  "Four-electron oxidation of p-hydroxylaminobenzoate to p-nitrobenzoate by a peroxodiferric complex in AurF from Streptomyces thioluteus," Proc. Natl. Acad. Sci., U. S. A., 2010, 107, 15722–15727.

Jiang, W.; Xie, J.; Varano, P. T.; Krebs, C.*; Bollinger, J. M., Jr.*  "Two Distinct Mechanisms of Inactivation of the Class Ic Ribonucleotide Reductase from Chlamydia trachomatis by Hydroxyurea: Implications for the Protein Gating of Inter-subunit Electron Transfer," Biochemistry, 2010, 49, 5340–5349.

Zhang, Y.; Zhu, X.; Torelli, A.; Lee, M.; Dzikovski, B.; Koralewski, R. M.; Wang, E.; Freed, J.; Krebs, C.; Ealick, S. E.*; Lin, H.*  "Diphthamide biosynthesis requires a SAM-dependent [4Fe-4S]-containing enzyme," Nature, 2010, 465, 891-896.

Grove, T. L.; Ahlum, J. H.; Sharma, P.; Krebs, C.*; Booker, S. J.*  "A Consensus Mechanism for Radical SAM-Dependent Dehydrogenation? BtrN Contains Two [4Fe–4S] Clusters," Biochemistry, 2010, 49, 3783-3785.

Lee, K.; Saleh, L.*; Anton, B. P.; Madinger, C. L.; Benner, J. S.; Iwig, D. F.; Roberts, R. J.;  Krebs, C.*; Booker, S. J.*  "Characterization of RimO, a New Member of the Methylthiotransferase Subclass of the Radical SAM Superfamily," Biochemistry, 2009, 48, 10162-10174.

Korneeva Korboukh, V.; Li, N.; Barr, E. W.; Bollinger, J. M., Jr.*; Krebs, C.*  "A Long-Lived, Substrate-Hydroxylating Peroxodi iron(III/III) Intermediate in the Amine Oxygenase, AurF, from Streptomyces thioluteus," J. Am. Chem. Soc., 2009, 131, 13608-13609.

Matthews, M. L.; Neumann, C. S.; Miles, L. A.; Grove, T. L.; Booker, S. J.; Krebs, C.*; Walsh, C. T.*; Bollinger, J. M., Jr.*  "Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2," Proc. Natl. Acad. Sci., U. S. A., 2009, 106, 17723-17728.

Matthews, M. L.; Krest, C. M.; Barr, E. W.; Vaillancourt, F. H.; Walsh, C. T.*; Green, M. T.*; Krebs, C.*; Bollinger, J. M., Jr.*  “Substrate-Triggered Formation and Remarkable Stability of the C- H Bond-Cleaving Chloroferryl Intermediate in the Aliphatic Halogenase, SyrB2,” Biochemistry, 2009, 48, 4331-4343

Chatterjee, A.; Li, Y.; Zhang, Y.; Grove, T. L.; Lee, M.; Krebs, C.; Booker, S. J.; Begley, T. P.*; Ealick, S. E.*  "Reconstitution of ThiC in Thiamine Pyrimidine Biosynthesis Expands the Radical SAM Superfamily," Nature Chem. Biol., 2008, 4, 758-765.

Eser, B.; Barr, E. W.; Frantom, P. A.; Saleh, L.; Bollinger, J. M., Jr.*; Krebs, C.*; Fitzpatrick, P. F.*  "Direct Spectroscopic Evidence for a High-Spin Fe(IV) Intermediate in Tyrosine Hydroxylase," J. Am. Chem. Soc., 2007, 129, 11334-11335.

Jiang, W.; Hoffart, L. M.; Krebs, C.*; Bollinger, J. M., Jr.*  "Direct Detection of a Mn(IV)/Fe(IV) Intermediate in Assembly of the Mn(IV)/Fe(III) Cofactor of Chlamydia trachomatis Ribonucleotide Reductase," Biochemistry 2007, 46, 8709-8716.

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.

Galonić, D. P.; Barr, E. W.; Walsh, C. T.*; Bollinger, J. M., Jr.*; Krebs, C.*  "Two Interconverting High-Spin Fe(IV) Intermediates in Aliphatic Chlorination by the Fe(II)- and α-Ketoglutarate-Dependent Halogenase CytC3," Nature Chem. Biol., 2007, 3, 113-116.

Hoffart, L. M.; Barr, E. W.; Guyer, R. B.; Bollinger, J. M., Jr.*; Krebs, C.*  "Direct Spectroscopic Detection of a C-H-Cleaving High-Spin Fe(IV) Complex in a Prolyl-4-Hydroxylase," Proc. Natl. Acad. Sci., U. S. A., 2006, 103, 14738-14743.

Xing, G.; Diao, Y.; Hoffart, L. M.; Barr, E. W.; Prabhu, K. S.; Arner, R. J.; Reddy, C. C.; Krebs, C.*; Bollinger, J. M., Jr.*  "Evidence for C-H cleavage by an iron-superoxide complex in the glycol cleavage reaction catalyzed by myo-inositol oxygenase," Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 6130-6135.

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 is the oxygen activation reaction of the Fe(II) and a-ketoglutarate(a-KG)-dependent dioxygenase enzyme family. These enzymes play important roles in biochemistry (oxygen sensing and initiation of response to hypoxia, DNA repair, biosynthesis of antibiotics, etc) and they are believed to operate by a common mechanism. In collaboration with the group of J. Martin Bollinger, Jr., we study one member of this class, taurine:a-KG dioxygenase (TauD), and we identified the first reaction intermediate observed in this class of enzymes. This species contains a Fe=O unit, in which the iron is formally in the oxidation state +IV in the high-spin (S= 2) configuration. This species is the key species that abstracts an H-atom from the substrate for subsequent hydroxylation.

Heme enzymes:

We study the electronic structure of several high-valent intermediates using 57Fe-Mössbauer spectroscopy in collaboration with the group of Michael T. Green.

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. For example, we study the enzyme lipoate synthase using 57Fe-Mössbauer spectroscopy with the group of Squire J. Booker.

Research Interests:

Biological

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

Spectroscopy
Chemical Biology