We are using X-ray crystallography as our main research tool to study proteins that are either involved in functional protein-protein interactions or are related to cellular signal transduction pathways.

The overall goal of our studies is to advance our understanding of the functions and structural interactions of modular protein domains in the context of multi-domain proteins that are involved in cell signaling networks.

Biography

• Post-doctoral Research Associate with Liang Tong, Columbia University


• Ph.D. in Chemistry, Karl Franzens Universität Graz, Austria, with Christoph Kratky: "X-ray and Neutron Diffraction Studies of B12 Coenzymes in Free and Enzyme Bound State"


• M.Sc. in Chemistry, Karl Franzens Universität Graz, Austria, with Christoph Kratky: "Solid State Reactions in Cob(II)alamin Crystals"

Institutions

Karl Franzens University Graz, Austria

Research Description

Ongoing projects include:

Structural Characterization of Ribosomal Protein L11 Methylation
The ribosomal protein L11 is positioned in the crucial GTPase associated region of the large subunit. L11 consists of two domains that are likely to adopt different conformations and act as a molecular switch during ribosomal protein synthesis. L11 also serves as the binding site for the thiazol class of bacterial antibiotics. In bacteria, L11 is methylated by the protein methyltransferase A. Neither the structural implications of this protein modification nor the functional consequences are fully understood. We are working to obtain complex structures for L11 and PrmA to characterize this methylation reaction and understand its relevance for ribosomal function.

Structural Biology of Autophagy
Autophagy has originally been described as a starvation response mechanism in yeast, where it serves to recycle large portions of cytosol and cellular organelles to prolong cellular survival in the absence of nutrients. Autophagic cell death has recently been described in neurodegenerative diseases such as Huntington's and Alzheimer's disease. A current model suggests that autophagy initially serves as a pro-survival mechanism that is activated to remove the increasing amounts of insoluble protein aggregates accumulating in the cell. At a later stage, this pro-survival mechanism is overwhelmed and autophagic cell death occurs. Pharmacologic intervention to inhibit autophagic cell death might therefore delay the progression of neurodegenerative diseases. We are studying the structural biology of autophagy to establish the molecular mechanism of this highly conserved pathway. A long-term goal of this project is to identify key enzymes of autophagy and evaluate their potential use as drug targets for the treatment of neurodegenerative diseases.

Inositolkinases and Phosphatidylinositol Signaling Pathways
Differential phosphorylation of phosphatidylinositol and inositol creates a perplexing number of compounds, which serve as cellular messenger in a variety of fundamental cellular processes (e.g., autophagy is regulated by the activity of a phosphatidylinositol 3-kinase.) The phosphorylation state of these inositolphosphates is regulated by a series of inositol specific kinases and phosphatases (with the most prominent members PI3K and PTEN). Despite their functional importance, there is comparatively little structural information available for these enzymes. We are interested in determining protein structures of inositolkinases to further increase our understanding of inositol based signal transduction pathways.

Awards

M.Sc. Thesis Award of the Austrian Chemical Society 1994

Affiliations

American Crystallographic Association
American Society for Biochemistry and Molecular Biology
American Association for the Advancement of Sciences
RNA Society
Protein Society

Funded Research

• 2008: Brown University Salomon Faculty Research Award


• 2006: Medical Research Award, Rhode Island Foundation
  01/06 $10,000


• 2006: Brown University Research Seed Fund (with Rebecca Page)
  Structural Biology and Function of Macromolecular Complexes: Using Light Scattering to Initiate the Establishment of a Brown University Facility for State-of-the-Art Protein Biophysical Characterization
  02/2006 $53,000

Courses Taught

• Current Topics in Biochemistry and Molecular Biology (BI0221)
• Current Topics in Biochemistry and Molecular Biology (BI0220)
• Independent Research (BI0195)
• Introductory Biochemistry (BI0028)

View My Full Publication List in pdf format

Selected Publications

• Demirci H, Belardinelli R, Seri E, Gregory ST, Gualerzi C, Dahlberg AE, Jogl G; Structural rearrangements in the active site of the Thermus thermophilus 16S rRNA methyltransferase KsgA in a binary complex with 5'-methylthioadenosine. J. Mol. Biol. 388, 271-282 (2009).(2009)
• Li H and Jogl G; Structural and biochemical studies of TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator). J. Biol. Chem. 284, 1748-1754 (2009).(2009)
• Gregory ST, Demirci H, Belardinelli R, Monshupanee T, Gualerzi C, Dahlberg AE, Jogl G; Structural and functional studies of the Thermus thermophilus 16S rRNA methyltransferase RsmG. RNA 15, 1693-1704 (2009).(2009)
• Demirci H, Gregory S, Dahlberg AE, Jogl G; Multiple site trimethylation of ribosomal protein L11 by the PrmA methyltransferase. Structure, 16, 1059-1066 (2008).(2008)
• Demirci H, Gregory S, Dahlberg AE, Jogl G; Crystal structure of the Thermus thermophilus 16S rRNA methyltransferase RsmC in complex with cofactor and substrate guanosine. J. Biol. Chem. 283, 26548-26556 (2008).(2008)
• Demirci H, Gregory S, Dahlberg A, Jogl G; Recognition of Ribosomal Protein L11 by the Protein Trimethyltransferase PrmA. EMBO J., 26, 567-577 (2007).(2007)
• Li H and Jogl G; Crystal Structure of the Zinc-binding Transport Protein ZnuA from Escherichia coli Reveals an Unexpected Variation in Metal Coordination. JMB, 368, 1358-1366 (2007).(2007)
• You Z, Omura S, Ikeda H, Cane DE, Jogl G; Crystal Structure of the Non-heme Iron Dioxygenase PtlH in Penatlenolactone Biosynthesis. J. Biol. Chem. 282, 36552-36560 (2007).(2007)
• Holmes W and Jogl G; Crystal Structure of Inositol Phosphate Multikinase 2 and Implications for Substrate Specificity. J. Biol. Chem., 281, 38109-38116 (2006)(2006)
• Jogl G, Hsiao Y, Tong L: Crystal structure of mouse carnitine octanoyltransferase and molecular determinants of substrate selectivity. J. Biol. Chem., 280, 738-744 (2005).(2005)
• Jogl G, Tong, L: Crystal structure of yeast acetyl-coenzyme A synthetase in complex with AMP. Biochemistry, 43, 1425-1431 (2004).(2004)
• Jogl G, Tong, L: Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport. Cell, 112, 113-122 (2003).(2003)
• Jogl G, Rozovsky S, McDermott AE, Tong, L: Optimal alignment for enzymatic proton transfer: Structure of the Michaelis complex of triosephosphate isomerase at 1.2Å resolution. Proc. Natl. Acad. Sci. USA, 100, 1, 50-55 (2003).(2003)
• Jogl G, Shen Y, Gebauer D, Li J, Wiegmann K, Kashkar H, Kronke M, Tong L: Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain. EMBO J., 21, 18, 4785-4795 (2002).(2002)