Biological

Biological Chemistry Seminar: Anna Pyle, Yale University

Thu, 2013-02-07 16:00
Location: 

Carolyn Hoff Lynch Room

Biological Chemistry Seminar: Howard Hang, Rockefeller University

Thu, 2013-01-31 16:00
Location: 

Carolyn Hoff Lynch Room

Biological Chemistry Seminar: Gino Segrè, University of Pennsylvania

Thu, 2013-01-24 16:00
Location: 

Carolyn Hoff Lynch Room

Biological Chemistry Seminar: Brad Pentelute, MIT

Thu, 2013-01-17 16:00
Location: 

Carolyn Hoff Lynch Room

Biological Chemistry Seminar: Douglas Cerasoli, U.S. Army

Thu, 2012-11-29 16:00
Location: 

Carolyn Hoff Lynch Room

Biological Chemistry Seminar: Elizabeth Boon, Stony Brook University

Thu, 2012-11-15 16:00
Location: 

Carolyn Hoff Lynch Room

Biological Chemistry Seminar: Emily Balskus, Harvard University

Thu, 2012-11-08 16:00
Speaker: 

Emily Balskus, Harvard University

Location: 

Carolyn Hoff Lynch Room

Donald Voet

Photo: 
First Name: 
Donald
Last Name: 
Voet
Official Title: 
Emeritus Associate Professor of Chemistry

Biological Chemistry

Contact Information
Office Location: 
349 N
Email: 
voet@sas.upenn.edu
Phone: 
(215) 898-6457
Education: 
  • 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

 

Emmanuel Skordalakes

Photo: 
First Name: 
Emmanuel
Last Name: 
Skordalakes
Official Title: 
Associate Professor, Gene Expression and Regulation Program

Biological Chemistry 

Additional Titles: 
Wistar Institute Associate Professor of Chemistry
Contact Information
Email: 
skorda@wistar.org
Phone: 
(215) 495-6884
Fax: 
(215) 573-9889
Education: 
  • 2001-2006: Postdoctoral Fellow, University of California, Berkeley
  • Ph.D.: Imperial College, University of London (2000)
  • M.Sc.: University College London (University of London) (1992)
  • B.Sc.: Anglia Ruskin University, Cambridge (1991)
Research Interests: 

 

The focus of my research lies with protein nucleic acid assemblies that participate in the replication and maintenance of eukaryotic chromosome ends, called telomeres. Telomeres protect chromosome ends from gradual length erosion, prevent end-to-end fusions and recombination, and promote proper chromosome partitioning during meiosis. Telomere length deregulation and telomerase activation are early and perhaps necessary steps in cancer cell evolution. Furthermore, telomerase and telomere dysfunction are thought to contribute to replicative senescence and programmed cell aging. Despite these fundamental roles in maintaining genome integrity and cell fate, surprisingly little is known about the molecular basis of telomere synthesis by telomerase. We are interested in elucidating the mechanism of telomere replication by telomerase and understand how telomere and telomerase binding proteins regulate telomerase activity and protect chromosome ends. The lab primarily uses structural methods coupled with biophysical and biochemical techniques to study the above systems.

Telomerase Function

Telomere replication is mediated by telomerase, an RNA dependent DNA polymerase structurally similar to retroviral reverse transcriptases and viral RNA polymerases. Biochemical studies on telomerase for more than two decades have provided a wealth of information regarding telomerase function and substrate specificity. Despite this information, the biophysical mechanisms underlying telomerase architecture and function are poorly understood. Our goal is to further elucidate the molecular basis of telomere replication by telomerase using structural and biochemical approaches. The information generated here should provide novel insights into the basic mechanisms of telomere replication and length homeostasis. It will further enrich our understanding of the mechanism of DNA replication by polymerases in general. It will provide a framework to design small molecule inhibitors of telomerase that may be of therapeutic value for cancer and other diseases associated with cellular aging.

Telomerase Regulation

In recent years, a number of factors essential for telomerase regulation and telomere maintenance have been identified. The method by which telomerase and associated regulatory factors physically interact and function with each other to maintain appropriate telomere length is poorly understood. Structural and biochemical characterization of these factors, both in isolation and in complex with one another will facilitate our understanding of how the proper function of these factors impacts telomerase function and cell proliferation.

Jeffery G. Saven

Photo: 
First Name: 
Jeffery G.
Last Name: 
Saven
Official Title: 
Professor of Chemistry

Biological and Theoretical Physical Chemistry

Contact Information
Office Location: 
266 Cret, Lab 261 Cret
Email: 
saven@sas.upenn.edu
Phone: 
215-573-6062
Fax: 
215-573-2112
Admin Support: 
Education: 
  • BA, New College of Florida
  • PhD, Columbia University & University of Wisconsin
  • NSF Postdoctoral Fellow in Chemistry, University of Illinois, Urbana-Champaign, 1993-1995. Postdoctoral Research Associate, University of Illinois, Urbana-Champaign, 1995-1997
Research Interests: 

Computationally designed protein complex containing a nonbiological cofactor, designed and studied in collaboration with the DeGrado and Therien groups in the Department of Chemistry. On the left is the computationally designed protein scaffold (magenta) and two abiotic porphyrin cofactors (yellow). On the right is a model of the computationally designed sequence and structure.

 

Our research interests involve theoretical chemistry, particularly as it applies to biopolymers, macromolecules, condensed phases, and disordered systems. We are developing computational methods for understanding and designing molecular sytems having many physical and chemical degrees of freedom. Molecular simulation techniques are used both to study molecular systems in detail and to test and illustrate our theories. 

 

A current thrust of the group involves developing computational tools for understanding the properties of protein sequences consistent with a chosen three-dimensional structure. The group works closely with experimental groups at Penn and at other universities; some group members are involved in joint theoretical/experimental projects. Recent projects involve the design of soluble and membrane bound proteins, discerning the origins of conservation in naturally occurring proteins, biomolecular simulation, and the design of nonbiological folding molecules.

Department of Chemistry

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

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

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