Angela M Gronenborn
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Phone (412) 648-9959
Fax (412) 648-9008

University of Pittsburgh
1050 Biomedical Science Tower 3

 

Angela Gronenborn

UPMC Rosalind Franklin Professor and Chair
Department of Structural Biology
Distinguished Professor of Structural Biology
University of Pittsburgh School of Medicine
Professor of Bioengineering
Swanson School of Engineering


Angela Gronenborn's research combines nuclear magnetic resonance (NMR) spectroscopy with biophysics, biochemistry, and chemistry to investigate cellular processes at the molecular and atomic levels in relation to human disease. We presently focus on two areas in biology: gene regulation and HIV pathogenesis. To understand how biological macromolecules work and intervene  with respect to activity and function, detailed knowledge of their architecture and dynamic features is required. Evaluation of the major determinants for stability and conformational specificity of normal and disease-causing forms of these molecules will allow us to unravel the complex processes associated with disease. Our group has developed new NMR methods for determining three-dimensional structures of biological macromolecules and applies these to challenging systems. Key contributions include the development of restrained molecular dynamics/simulated annealing algorithms and multidimensional, heteronuclear spectroscopy, which allowed the extension of conventional NMR methods to higher molecular weight systems. The Gronenborn group has solved solution structures of a large number of medically and biologically important proteins, including cytokines and chemokines, transcription factors and their complexes and various HIV and AIDS related proteins. Work is also carried out on protein folding and design using the model protein GB1.

Visit Angela's lab website


Education & Training

Undergraduate
University of Cologne, Cologne, Germany
Vordiplom, 1972 in Chemistry, Physics

Postgraduate
University of Cologne, Cologne, Germany
Diplom (MS), 1975 in Chemistry

University of Cologne, Cologne, Germany
Dr.rer.nat. (PhD), 1978, summa cum laude, in Organic Chemistry

National Institute for Medical Research, Mill Hill, London
Division of Molecular Pharmacology, Advisor:  James Feeney


Selected Awards and Honors


2006 EAS Award for Excellence in Magnetic Resonance

2007 Elected to Membership in the National Academy of Sciences

2010 Elected to the Norwegian Academy of Science and Letters

2014 Life Science Award, Carnegie Science Awards

2014 Elected to the Germany Academy of Sciences Leopoldina

2018 Elected to the American Academy of Arts and Sciences
2018 American Society for Biochemistry and Molecular Biology Mildred Cohn Award in Biological Chemistry



Representative Publications


Gronenborn AM, Birdsall B, Hyde EI, Roberts GCK, Feeney J, Burgen ASV.  Direct observation by NMR of two coexisting conformations of an enzyme-ligand complex in solution.  Nature 230, 273 (1980).

 

Oschkinat H, Griesinger C, Kraulis PJ, Sørensen OW, Ernst RR, Gronenborn AM, Clore GM. Three-dimensional NMR spectroscopy of a protein in solution. Nature 332, 374 (1988).

 

Clore GM, Gronenborn AM.  Structures of larger proteins in solution: three- and four-dimensional heteronuclear NMR spectroscopy. Science 252, 1390 (1991).

 

Omichinski JG, Clore GM, Schaad O, Felsenfeld G, Traino, C, Appella E, Stahl SJ, Gronenborn AM.   NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science 261, 438-446 (1993).

 

Frank MK, Dyda F, Dobrodumov A, Gronenborn AM.  Core mutations switch monomeric protein GB1 into an intertwined tetramer.  Nat. Struct. Biol., 9(11): 877-885 (2002).

 

Byeon, IL, Meng X, Jung J, Zhao G, Yang R, Ahn J, Shi J, Concel J, Aiken C, Zhang P, Gronenborn AM. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 139, 780 (2009). PMC2782912

 

Ahn J, Vu T, Novince Z, Guerrero-Santoro J, Rapic-Otrin V, Gronenborn AM. HIV-1 Vpr loads Uracil DNA Glycosylase-2 onto DCAF1, a substrate recognition subunit of a Cullin 4A-RING E3 ubiquitin ligase for proteasome-dependent degradation. J Biol Chem 285, 37333 (2010). PMC2988339

 

Byeon I-JL, Ahn J, Mitra, M, Byeon C-H, Hercik, K, Hritz J, Charlton LM, Levin JG, Gronenborn AM.  NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity.  Nature Comm 4 1890 (2013). PMC3674325

 

Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics.  Nature 497, 643 (2013). PMC3729984

 

Boatz JC, Whitley MJ, Li M, Gronenborn AM, van der Wel PCA. Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH.   Nat Commun. 8:15137 (2017).  PMC5424181 

 

Wang M, Quinn CM, Perilla JR, Zhang H, Shirra R Jr, Hou G, Byeon IJ, Suiter CL, Ablan S, Urano E, Nitz TJ, Aiken C, Freed EO, Zhang P, Schulten K, Gronenborn AM, Polenova T. Quenching protein dynamics interferes with HIV capsid maturation.  Nat Commun. 8:1779 (2017).  PMC5701193
 

Lu M, Sarkar S, Wang M, Kraus J, Fritz M, Quinn CM, Bai S, Holmes ST, Dybowski C, Yap GPA, Struppe J, Sergeyev IV, Maas W, Gronenborn AM, Polenova T. 19F Magic Angle Spinning NMR Spectroscopy and Density Functional Theory Calculations of Fluorosubstituted Tryptophans: Integrating Experiment and Theory for Accurate Determination of Chemical Shift Tensors.  J Phys Chem B.122:6148 (2018).  

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Active Grants


University of Pittsburgh Center for HIV Protein Interactions (PCHPI)

08/27/2007 to 7/31/22

National Institutes of Health

P50

 

Allosteric regulation of SIRT1 by a PACS-2 and DBC1 regulatory hub

08/23/2017 to 6/30/21

National Institutes of Health

R01

 

Development of Fluorine Nuclear Magnetic Resonance (NMR) Spectroscopy as a Versatile Probe of Structure and Chemical Environment in Proteins

08/01/2017 to 7/31/21
National Science Foundation