Carsten Krebs

About

Carsten Krebs is a Distinguished Professor of Chemistry and Biochemistry and Molecular Biology at Pennsylvania State University, serving also as the Associate Department Head for Chemistry Climate and Diversity. His research focuses on bioinorganic chemistry, specifically spectroscopic and kinetic studies on the mechanisms of iron-containing enzymes. His interdisciplinary program aims to combine biochemical, kinetic, and spectroscopic methods, primarily utilizing 57Fe-Mössbauer spectroscopy, to study iron enzymes that play vital roles in various biological processes. Krebs's work extensively investigates enzymes that utilize non-heme iron cofactors to activate dioxygen for oxidation reactions, as well as enzymes containing iron-sulfur clusters, such as Radical-SAM enzymes. His research provides detailed insights into the reaction mechanisms of these enzymes, including the characterization of reaction intermediates and the understanding of their structural and functional diversity. His contributions have advanced the understanding of iron's role in enzymatic catalysis, with implications for biochemistry and potential applications in medicine and biotechnology.

Research topics

• Chemistry
• Biochemistry
• Stereochemistry
• Biology
• Photochemistry
• Virology
• Organic chemistry
• Internal medicine
• Medicinal chemistry

Selected publications

• Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets

  Science · 2021 · 126 citations

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. We found that the catalytic subunit of the RdRp, nsp12, ligates two iron-sulfur metal cofactors in sites that were modeled as zinc centers in the available cryo-electron microscopy structures of the RdRp complex. These metal binding sites are essential for replication and for interaction with…

  DOI

• A Peroxodiiron(III/III) Intermediate Mediating Both <i>N</i> -Hydroxylation Steps in Biosynthesis of the <i>N</i> -Nitrosourea Pharmacophore of Streptozotocin by the Multi-domain Metalloenzyme SznF

  Journal of the American Chemical Society · 2020 · 81 citations

  xidases and oxygenases (HDOs).

  DOI

• Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase

  Nature Communications · 2020 · 71 citations

  ] cluster acquisition and coordination. The enzymatic activity of human ALAD is greatly reduced upon loss of its Fe-S cluster, which results in reduced heme biosynthesis in human cells. As ALAD provides an early Fe-S-dependent checkpoint in the heme biosynthetic pathway, our findings help explain why heme biosynthesis depends on intact ISC biogenesis.

  DOI

• An iron–sulfur cluster in the zinc-binding domain of the SARS-CoV-2 helicase modulates its RNA-binding and -unwinding activities

  Proceedings of the National Academy of Sciences · 2023-08-08 · 47 citations

  articleOpen access

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, uses an RNA-dependent RNA polymerase along with several accessory factors to replicate its genome and transcribe its genes. Nonstructural protein (nsp) 13 is a helicase required for viral replication. Here, we found that nsp13 ligates iron, in addition to zinc, when purified anoxically. Using inductively coupled plasma mass spectrometry, UV-visible absorption, EPR, and Mössbauer spectroscopies, we char…

  PublisherOA PDFDOI

• An Iron(IV)–Oxo Intermediate Initiating <scp>l</scp>-Arginine Oxidation but Not Ethylene Production by the 2-Oxoglutarate-Dependent Oxygenase, Ethylene-Forming Enzyme

  Journal of the American Chemical Society · 2021 · 47 citations

  ]-l-Arg slows decay of the ferryl complex by >16-fold, implying that RO is initiated by hydrogen-atom transfer (HAT) from C5. That this large substrate deuterium kinetic isotope effect has no impact on the EF:RO partition ratio implies that the same ferryl intermediate cannot be on the EF pathway; the pathways must diverge earlier. Consistent with this conclusion, the variant enzyme bearing the Asp191Glu ligand substitution accumulates ∼4 times as much of the ferryl complex as the wild-type enzy…

  DOI

Recent grants

• NIH Grant R01GM103268

  NIH · $1.3M · 2017

• Structure and function of intermediates involved in metalloenzymatic N-oygenation and oxidation reactions

  NSF · $390k · 2011–2015

• Mechanisms and Reprogramming of Iron/2-Oxoglutarate Desaturases and Oxacyclases

  NIH · $1.0M · 2016–2021

Frequent coauthors

• J. Martin Bollinger

  Pennsylvania State University

  211 shared

• Boi Hanh Huynh

  181 shared

• Wei Jiang

  76 shared

• Dale E. Edmondson

  Emory University

  54 shared

• Eric W. Barr

  University of Pennsylvania

  48 shared

• Laura M. K. Dassama

  Stanford Medicine

  47 shared

• Alice S. Pereira

  46 shared

• Stephen J. Lippard

  45 shared

Awards & honors

• Elected Fellow of the American Association for the Advanceme…
• 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)

Similar researchers at Pennsylvania State University

• Ayusman Senh-96
• Raymond Schaakh-80
• Harry Allcockh-79