Chemical Biology

Special Seminar: Sharon Aviran, University of California, Berkeley

Thu, 2013-01-24 10:00

Dr. Sharon Aviran

University of California, Berkeley


High-throughput RNA structure analysis from chemical footprinting experiments


Host: Randy Kamien (Physics)


Lynch Lecture Hall


New regulatory roles continue to emerge for both natural and engineered RNAs, many of which have specific structures essential to their function. This highlights a growing need to develop technologies that enable rapid and accurate characterization of structural features within complex RNA populations. Yet, available techniques that are reliable are also vastly limited by technological constraints, while the accuracy of popular computational methods is generally poor. These limitations thus pose a major barrier to comprehensive determination of structure from sequence.

Special Seminar: Kirill Korolev, MIT

Tue, 2013-01-22 10:00

Dr. Kirill Korolev

Massachusetts Institute of Chemistry


The interplay between ecology and evolution in cancerous tumors and expanding populations


Host: Andrea Liu


Lynch Lecture Hall


Special Seminar: Eleni Katifori, MPI-Goettingen

Thu, 2013-01-17 10:00

Dr. Eleni Katifori

Max Planck Institute - Goettingen


The evolution of leaf vasculature: deciphering the design of optimal loopy architectures


Host: Douglas Jerolmack (Earth and Environmental Sciences)


Lynch Lecture Hall


Hirschmann Visiting Professor Lecture 1 - James Skinner, Univ. Wisconsin

Tue, 2013-02-19 16:00

James L. Skinner, University of Wisconsin, Madison


Lecture 1

The mystery of water and its phases
Tuesday, February 19, 2013
4:00 PM
Reception to follow in Nobel Hall


Carolyn Lynch Lecture Hall

Chemical Biophysics Mini-Symposium

Thu, 2013-01-10 12:30 - 17:30


Speakers include: 


Steven Artandi

Stanford University


Lorena Beese

Duke University


Robert Weinberg

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology


Cynthia Wolberger

Howard Hughes Medical Institute, The Johns Hopkins University



Lynch Lecture Hall, Chemistry Building


Topic: The Chemical Biology of Cancer


Click here for more details.


Elizabeth Rhoades, Yale; Special Biophysical Seminar

Fri, 2012-12-07 13:00

Elizabeth Rhoades, Yale University


Where the Crystal Structure Ends:  Defining 'Structure' in Disordered Proteins


Lynch Lecture Hall

Donald Voet

First Name: 
Last Name: 
Official Title: 
Emeritus Associate Professor of Chemistry

Biological Chemistry

Contact Information
Office Location: 
349 N
(215) 898-6457
  • B.S. California Institute of Technology (1960)
  • Ph.D. Harvard University (1967)
  • Post Doc at MIT, Cambridge, MA, 1966–1969 in the laboratory of Alexander Rich
  • Member ACS and AAAS
  • Visiting Scholar, Weizmann Institute of Science, Rehovot, Israel, 1993 and 1998
  • Editor-in-Chief, Biochemical and Molecular Biology Education.
Research Interests: 

We are studying the structures of biologically interesting molecules by X-ray crystallography in an effort to understand their structure-function relationships. Current projects include:


Yeast inorganic pyrophosphatase

Pyrophosphatases are essential enzymes that catalyze the hydrolysis of inorganic pyrophosphate to phosphate and, in doing so, drive the many biosynthetic reactions that yield pyrophosphate (e.g., polypeptide and polynucleotide synthesis) to completion. We have determined the refined 2.7-angstrom resolution structure of yeast inorganic pyrophosphatase, a dimeric enzyme of identical 286-residue subunits. We are presently determining the X-ray structures of selected mutant forms of this enzyme, both alone and in complex with inhibitors of this enzyme. The results of these studies, when correlated with the enzymological characteristics of the mutant enzymes, should lead to the formulation of a catalytic mechanism of inorganic pyrophosphatases as well as a greater understanding of biological phosphoryl transfer reactions in general.


Granulocyte -macrophage colony-stimulating factor (GM-CSF)

GM-CSF is a protein growth factor (cytokine) that stimulate the differentiation, proliferation, and activation of white blood cells known as granulocytes and macrophages. The therapeutic use of GM-CSF therefore holds considerable promise for the treatment of immunosuppressive conditions such as AIDS and the consequences of cancer chemotherapy. Indeed, GM-CSF is presently in clinical use to facilitate bone marrow transplantation. We have determined the refined X-ray structure of human GM-CSF to 3.0-angstrom resolution. We plan to determine the X-ray structures of selected mutant varieties of human GM-CSF in an effort to understand how GM-CSF interacts with its cell surface receptor. We also intend to determine the X-ray structure of the human GM-CSF receptor, both alone and in complex with GM-CSF. 



The x-ray structure of yeast inorganic pyrophosphatase. A 286-residue monomer unit of this homodimeric enzyme is shown with its polypeptide backbone represented in ribbon form embedded in its solvent accessible surface. The side chains of its active site residues are shown in ball-and-stick form.

Selected Publications: 

Voet , Voet; Biochemistry, 3rd Edition Student Companion Site

E. James Petersson

First Name: 
E. James
Last Name: 
Official Title: 
Associate Professor of Chemistry
Contact Information
Office Location: 
350 N
Admin Support: 

• A.B. Dartmouth College (1998)

• Ph.D. California Institute of Technology (2005)

• NIH Postdoctoral Fellow, Yale University (2005-2008)

• Searle Scholar (2010)

• Sloan Research Fellow (2012)

• NSF CAREER Award (2012)

• Award for Early Excellence in Physical Organic Chemistry      (2013)

Research Interests: 

Protein motion underlies both proper function and disease in biological systems. Many signaling and transport proteins require complex rearrangements for function, and some proteins, such as amyloids, misfold into toxic conformations. Studying these protein motions not only aids our understanding of diverse biological phenomena, it also contributes to an important fundamental problem in biochemistry: understanding how motions propagate from one end of a protein to another. The Petersson laboratory is developing tools to address questions of how dynamic proteins mediate communication and how the cellular environment catalyzes protein misfolding, from detailed in vitro folding studies to modeling protein motion in living cells. These tools include novel chromophores, which we synthesize and incorporate into proteins through unnatural amino acid mutagenesis and synthetic protein ligation.

Selected Publications: 

Inteins as Traceless Purification Tags for Unnatural Amino Acid Proteins

Batjargal, S.; Walters, C. R.; Petersson, E. J.

J. Am. Chem. Soc. 2015, 137, 1734-1737.


Specific Modulation of Protein Activity Through a Bioorthogonal Reaction

Warner, J. B.; Muthusamy, A. K.; Petersson, E. J.

ChemBioChem 2014, 24, 2508-2514.


Thioamide-Based Fluorescent Protease Sensors

Goldberg, J. M.; Chen, X. S.; Meinhardt, N.; Greenbaum, D. C.; Petersson, E. J. 

J. Am. Chem. Soc. 2014, 136, 2086-2093.


Efficient Synthesis and In Vivo Incorporation of Acridonylalanine, a Fluorescent Amino Acid for Lifetime and Förster Resonance Energy Transfer/Luminescence Resonance Energy Transfer Studies 

Speight, L. C.; Muthusamy, A. K.; Goldberg, J. M.; Warner, J. B.; Wissner, R. F.; Willi, T.; Woodman, B.; Mehl, R. A.; Petersson,     E. J. 

J. Am. Chem. Soc. 2013, 135, 18806-18814.


Expressed Protein Ligation at Methionine: N-terminal Attachment of Homocysteine, Ligation, and Masking

Tanaka, T.; Wagner, A. M.; Warner, J. B.; Wang, Y. J.; Petersson, E. J. 

Angew. Chem. Int. Ed. 2013, 52, 6210-6213.


Labeling Proteins with Fluorophore/Thioamide FRET Pairs by Combining Unnatural Amino Acid Mutagenesis and Native Chemical Ligation

Wissner, R. F.; Batjargal, S.; Fadzen, C. M.; Petersson, E. J. 

J. Am. Chem. Soc. 2013, 135, 6529-6540.


Thioamide Quenching of Fluorescent Probes Through Photoinduced Electron Transfer: Mechanistic Studies and Applications

Goldberg, J. M.; Batjargal, S.; Chen, B. S.; Petersson, E. J. 

J. Am. Chem. Soc. 2013, 135, 18651-18658.

Ronen Marmorstein

First Name: 
Last Name: 
Official Title: 
Professor, Department of Biochemistry and Biophysics Investigator, Abramson Family Cancer Research Institute

Biological Chemistry

Additional Titles: 
Wistar Institute Professor of Chemistry
Contact Information
Office Location: 
BRB II/III, Room 454
  • B.S. University of California at Davis (1984)
  • M.S. University of Chicago (1989)
  • Ph.D. University of Chicago (1989)
  • Postdoctoral Fellow, Harvard University (1989-1994)
Research Interests: 

The laboratory uses a broad range of molecular, biochemical and biophysical research tools centered around X-ray crystal structure determination to understand the mechanism of chromatin recognition and assembly and post-translational histone and protein modification in the regulation of gene expression; and kinase signaling pathways. The laboratory is particularly interested in gene regulatory proteins and their upstream signaling kinases that are aberrantly regulated in cancer and age-related metabolic disorders such as type II diabetes and obesity, and the use of high-throughput small molecule screening and structure-based design strategies towards the development of protein-specific small-molecule probes to be used to further interrogate protein function and for development into therapeutic agents.

Chromatin recognition and assembly and histone modification in gene regulation. DNA within the eukaryotic nucleus is compacted into chromatin containing histone proteins and its appropriate regulation orchestrates all DNA-templated reactions such as DNA transcription, replication, repair, mitosis, and apoptosis. Among the many proteins that regulate chromatin, the proteins that recognize DNA, assemble chromatin, called histone chaperones, and that modify the histones through the addition or removal of functional groups such as acetyl, methyl or phosphate play important roles. We are studying the DNA binding proteins p53, FoxO and the Gal4 family; the histone chaperones HIRA, Asf1, Vps75 and their associated factors; and the family of histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes. We are particularly interested in how DNA binding proteins navigate the recognition of their cognate DNA targets, how histone chaperones coordinate the assembly of distinct chromatin complexes correlated with different DNA regulatory processes, and how histone modification enzymes link catalysis to their substrate specific activities for their respective biological activities. More recently, we have been studying how the binding of accessory and regulatory protein subunits regulates the various activities of these proteins and in some cases we are developing small molecule protein specific inhibitors.


Enzymes associated with aging and age-related disorders.Sirtuin enzymes are NAD+-dependent histone and protein deactylases and/or ADP-ribotransferases that have been implicated in the regulation of gene expression, cellular aging, adipogenesis, type II diabetes and several neurodegenerative disorders. We have determined the structure of these enzymes in several liganded forms and have developed novel small molecule sirtuin inhibitors. Together with associated biochemical studies, these studies have provided insights into the mode of catalysis and substrate-specific recognition by this protein family and have illuminated new avenues for small molecule effector design. We are currently working towards understanding the factors that distinguish different sirtuin proteins and how the functions of these proteins are modulated by other protein factors. We are also pursuing structure/function studies of other proteins that are implicated in aging and age-related disorders.


Tumor suppressors and oncoproteins. We are carrying out biochemical and structural studies on the tumor suppressor proteins pRb, p53 and p300/CBP, both alone and in complex with their relevant protein targets. We are also interested in the mode of inactivation of these tumor suppressors by the viral oncoproteins E7 and E6 from human papillomavirus (HPV), the etiological agent for cervical cancer, and Adenovirus (Ad) E1A. We are also combining structural studies with small molecule screening to prepare small molecule HPV-E7 and for HPV-E6 inhibitors. Most recently we have begun to exploit structure-based design strategies to develop inhibitors of oncogenic kinases, such as PI3K, BRAF and PAK1 implicated in melanoma and other cancers. Our goal for these studies is to derive functional and structural information that will lead to the design of small molecule compounds that may have therapeutic applications.

Tumor suppressors and viral oncoproteins- We are pursuing biochemical and structural studies on the tumor suppressor proteins p18INK4c, pRb, p53 and p300/CBP, both alone and in complex with their relevant protein targets. The activity of pRb is inhibited by several known DNA viral oncoproteins, including human papillomavirus (HPV) E7, the etiological agent for cervical cancer, and Adenovirus (Ad) E1A. We have most recently characterized the binding properties of pRb to HPV-E7 and Ad-E1a and are now determining their structures both alone and in complex with pRb. Our goal for these studies is to derive functional and structural information that will lead to the design of small molecule compounds that may have clinical applications against cancer.


Protein-DNA recognition- As a model to understand sequence-specific DNA recognition by transcriptional regulatory proteins, we are studying the structure and function of three families of DNA binding proteins, the fungal specific Zn2Cys6 binuclear cluster proteins, the higher eukaryotic Ets proteins and p53. We have determined several structures of these proteins either alone or in complex with their associated DNA targets and are continuing to use these proteins as a model to understand DNA recognition by protein and protein complexes. With regard to p53, we are studying its unique mode of DNA recognition and are developing structure-based strategies for the repair of tumor-derived p53 mutations.

Other Affiliations: 

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax |

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