Fred Dyda, Ph.D. : NIDDK

Fred Dyda, Ph.D.

NIDDK, National Institutes of Health
Building 5, Room 303
5 Memorial Dr.
Bethesda, MD 20892-0560
Tel: 301-402-4496
Fax: 301-496-0201

Research Website:

Education / Previous Training and Experience:
B.S., Eötvös Lóránd University, Hungary, 1986
Ph.D., University of Pittsburgh, 1992

Research Statement:

The current focus of the lab is to understand the molecular details of mechanisms by which protein activity can be modulated. To function properly, cells must coordinate and choreograph a large number of simultaneous events and processes. These are carried out by proteins. We use X-ray crystallography as our main tool to study the fine details of how the activity and function of protein-protein and protein-DNA complexes are regulated. We employ this approach as it is one of the few experimental techniques that produces high-resolution "snapshots" to visualize subtle changes in protein structure that often accompany functional regulation. With these snapshots in hand, we use a variety of biochemical, biophysical and simulation approaches to bridge the structures and biological function. For example, we are investigating how the movement of mobile genetic elements such as transposons or viruses is controlled. One of our current areas of emphasis is the Rep protein of adeno-associated virus (AAV); this protein catalyzes the integration of the AAV genome into a specific locus in human chromosome 19, making it an extremely useful tool for gene therapy studies. In addition, we are studying how a ubiquitous group of chaperone proteins known as 14-3-3s are able to direct when and where in a cell to deliver proteins that regulate gene expression.For more information, see my group on the Structural Biology Section home page.

Selected Publications:

Wickner RB, Dyda F, Tycko R Amyloid of Rnq1p, the basis of the [PIN+] prion, has a parallel in-register {beta}-sheet structure. Proc Natl Acad Sci U S A, 2008. [Full Text/Abstract]

Guynet C, Hickman AB, Barabas O, Dyda F, Chandler M, Ton-Hoang B In Vitro Reconstitution of a Single-Stranded Transposition Mechanism of IS608. Mol Cell(29): 302-312, 2008. [Full Text/Abstract]

Barabas O, Ronning DR, Guynet C, Hickman AB, Ton-Hoang B, Chandler M, Dyda F Mechanism of IS200/IS605 Family DNA Transposases: Activation and Transposon-Directed Target Site Selection. Cell(132): 208-20, 2008. [Full Text/Abstract]

Obsilova V, Nedbalkova E, Silhan J, Boura E, Herman P, Vecer J, Sulc M, Teisinger J, Dyda F, Obsil T The 14-3-3 Protein Affects the Conformation of the Regulatory Domain of Human Tyrosine Hydroxylase. Biochemistry(47): 1768-1777, 2008. [Full Text/Abstract]

Bradley CM, Jones S, Huang Y, Suzuki Y, Kvaratskhelia M, Hickman AB, Craigie R, Dyda F Structural basis for dimerization of LAP2alpha, a component of the nuclear lamina. Structure(15): 643-53, 2007. [Full Text/Abstract]

Ronning DR, Guynet C, Ton-Hoang B, Perez ZN, Ghirlando R, Chandler M, Dyda F Active site sharing and subterminal hairpin recognition in a new class of DNA transposases. Mol Cell (20): 143-54, 2005. [Full Text/Abstract]

Hickman AB, Dyda F Binding and unwinding: SF3 viral helicases. Curr Opin Struct Biol (15): 77-85, 2005. [Full Text/Abstract]

Hickman AB, Perez ZN, Zhou L, Musingarimi P, Ghirlando R, Hinshaw JE, Craig NL, Dyda F Molecular architecture of a eukaryotic DNA transposase. Nat Struct Mol Biol (12): 715-21, 2005. [Full Text/Abstract]

Bradley CM, Ronning DR, Ghirlando R, Craigie R, Dyda F Structural basis for DNA bridging by barrier-to-autointegration factor. Nat Struct Mol Biol (12): 935-6, 2005. [Full Text/Abstract]

Ton-Hoang B, Guynet C, Ronning DR, Cointin-Marty B, Dyda F, Chandler M Transposition of ISHp608, member of an unusual family of bacterial insertion sequences. EMBO J (24): 3325-38, 2005. [Full Text/Abstract]

Ronning DR Li Y Perez ZN Ross PD Hickman AB Craig NL Dyda F The carboxy-terminal portion of TnsC activates the Tn7 transposase through a specific interaction with TnsA. EMBO J , 2004. [Full Text/Abstract]

Hickman, A. B., Ronning, D.R., Perez, Z. N., Kotin, R. M., Dyda, F. The Nuclease Domain of the Adeno-Associated Virus Rep Coordinates Replication Initiation Using Two Distinct DNA Recognition Interfaces Molecular Cell(13): 403-414, 2004.

Zhou L, Mitra R, Atkinson PW, Hickman AB, Dyda F, Craig NL Transposition of hAT elements links transposable elements and V(D)J recombination. Nature (432): 995-1001, 2004. [Full Text/Abstract]

Klein DC Ganguly S Coon SL Shi Q Gaildrat P Morin F Weller JL Obsil T Hickman A Dyda F 14-3-3 proteins in pineal photoneuroendocrine transduction: how many roles? J Neuroendocrinol (15): 370-7, 2003. [Full Text/Abstract]

Dyda F Hickman AB A mob of reps. Structure (Camb) (11): 1310-1, 2003. [Full Text/Abstract]

Obsil T Ghirlando R Anderson DE Hickman AB Dyda F Two 14-3-3 binding motifs are required for stable association of Forkhead transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding. Biochemistry (42): 15264-72, 2003. [Full Text/Abstract]

Kirsten Frank M Dyda F Dobrodumov A Gronenborn AM Core mutations switch monomeric protein GB1 into an intertwined tetramer. Nat Struct Biol (9): 877-85, 2002. [Full Text/Abstract]

Hickman AB Ronning DR Kotin RM Dyda F Structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep. Mol Cell (10): 327-37, 2002. [Full Text/Abstract]

Obsil T Ghirlando R Klein DC Ganguly S Dyda F Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation. Cell (105): 257-67, 2001. [Full Text/Abstract]

Balbach JJ Ishii Y Antzutkin ON Leapman RD Rizzo NW Dyda F Reed J Tycko R Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer''s beta-amyloid peptide, and structural characterization by solid state NMR. Biochemistry (39): 13748-59, 2000. [Full Text/Abstract]

Dyda F Klein DC Hickman AB GCN5-related N-acetyltransferases: a structural overview. Annu Rev Biophys Biomol Struct (29): 81-103, 2000. [Full Text/Abstract]

Hickman AB Li Y Mathew SV May EW Craig NL Dyda F Unexpected structural diversity in DNA recombination: the restriction endonuclease connection. Mol Cell (5): 1025-34, 2000. [Full Text/Abstract]

Hickman AB Klein DC Dyda F Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism. Mol Cell (3): 23-32, 1999. [Full Text/Abstract]

Hickman AB Namboodiri MA Klein DC Dyda F The structural basis of ordered substrate binding by serotonin N-acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate analog. Cell (97): 361-9, 1999. [Full Text/Abstract]

Hickman AB Namboodiri MA Klein DC Dyda F The structural basis of ordered substrate binding by serotonin N-acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate analog. Cell (97): 361-9, 1999. [Full Text/Abstract]

Hickman AB Dyda F Craigie R Heterogeneity in recombinant HIV-1 integrase corrected by site-directed mutagenesis: the identification and elimination of a protease cleavage site. Protein Eng (10): 601-6, 1997. [Full Text/Abstract]

Hickman AB Waninger S Scocca JJ Dyda F Molecular organization in site-specific recombination: the catalytic domain of bacteriophage HP1 integrase at 2.7 A resolution. Cell (89): 227-37, 1997. [Full Text/Abstract]

Engelman A Liu Y Chen H Farzan M Dyda F Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase. J Virol (71): 3507-14, 1997. [Full Text/Abstract]

Li M Dyda F Benhar I Pastan I Davies DR Crystal structure of the catalytic domain of Pseudomonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: implications for the activation process and for ADP ribosylation. Proc Natl Acad Sci U S A (93): 6902-6, 1996. [Full Text/Abstract]

Arjunan P Umland T Dyda F Swaminathan S Furey W Sax M Farrenkopf B Gao Y Zhang D Jordan F Crystal structure of the thiamin diphosphate-dependent enzyme pyruvate decarboxylase from the yeast Saccharomyces cerevisiae at 2.3 A resolution. J Mol Biol (256): 590-600, 1996. [Full Text/Abstract]

Jenkins TM Hickman AB Dyda F Ghirlando R Davies DR Craigie R Catalytic domain of human immunodeficiency virus type 1 integrase: identification of a soluble mutant by systematic replacement of hydrophobic residues. Proc Natl Acad Sci U S A (92): 6057-61, 1995. [Full Text/Abstract]

Li M Dyda F Benhar I Pastan I Davies DR The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin. Proc Natl Acad Sci U S A (92): 9308-12, 1995. [Full Text/Abstract]

Dyda F Hickman AB Jenkins TM Engelman A Craigie R Davies DR Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science (266): 1981-6, 1994. [Full Text/Abstract]

Dyda F Furey W Swaminathan S Sax M Farrenkopf B Jordan F Catalytic centers in the thiamin diphosphate dependent enzyme pyruvate decarboxylase at 2.4-A resolution. Biochemistry (32): 6165-70, 1993. [Full Text/Abstract]

Page last updated: December 15, 2008

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