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Frances A. Jurnak

Professor, Physiology & Biophysics
School of Medicine

PH.D., University of California, Berkeley, Chemistry

Phone: (949) 824-6623, 4625
Fax: (949) 824-8540
Email: jurnak@uci.edu

University of California, Irvine
D350, D310 MED SCI I
Irvine, CA 92697


Research
Interests
Macromolecular crystallography;
protein structure;
elongation factor Tu;
pectate lyase
   
URL zeus.biomol.uci.edu/franjurnak.html
   
Academic
Distinctions
Dupont Lecturer, UC Berkeley, 1995
   
Research
Abstract
Model G Protein System: Elongation Factor Tu Complexes


The long term objective of my research program is the determination of the structural changes in EF-Tu as the protein carries out its role in polypeptide elongation. During protein synthesis, EF-Tu undergoes a series of conformational changes as it interacts with various cellular substrates including GDP, GTP, aminoacyl-tRNA and elongation factor, Ts. Several antibiotics are known to disrupt the normal elongation cycle by interacting with EF-Tu directly. Over the last twenty years, the structures of four cytoplasmic EF-Tu complexes have been determined by several laboratories. My laboratory has determined the structures of two: EF-Tu-GDP and EF-Tu-Ts at atomic resolution. Now that the conformational changes have been delineated for the cytoplasmic forms, the lab has initiated structural research to elucidate how EF-Tu interacts with various ribosomal components, including proteins and tRNA. The laboratory is also actively pursuing the x-ray diffraction analyses of five EF-Tu-antibiotic complexes in order to determine where and how the antibiotics interfere with the normal EF-Tu-ribosomal interaction. The atomic information will ultimately be used to rationally alter the antibiotic structures using computer graphics with the goal of creating more effective, less toxic drugs. The first complex to be solved is that of a complex between EF-Tu-GDP and tetracycline. The results demonstrate that the active region of tetracycline has a remarkable molecular fit to the invariant groups found in the GTPase center of EF-Tu as well as in many other nucleotide-binding proteins. Not only do the results call into question the validity of the textbook mode of tetracycline inhibition but provide the starting parameters for designing antibiotics to overcome the known resistance mechanisms as well as to inhibit specific targets of nucleotide-binding proteins. Moreover, many pharmacological agents, such as daunorubicin, share chemical similarities with the phenolidiketone moiety of tetracycline. The similarities suggest that tetracycline's mode of interactions with EF-Tu may represent a common binding motif responsible for primary or secondary physiological effects of related drugs.


Plant Virulence Factors


In recent years, the laboratory has embarked on a second research program, that of characterizing a family of plant virulence factors termed pectate lyases. The enzymes are known to cleave the polygalacturonic acid component of plant cell walls, causing "soft-rot" diseases in numerous crops. The three-dimensional structures of two pectate lyases, PelC and PelE, have been determined to a resolution of 2.2 Ã…. The enzymes fold into a unique domain motif consisting of all parallel beta strands coiled into a large right-handed helix. Within the core, the amino acids form linear stacks, which include a novel asparagine ladder. The pectate lyases are known sequence homologues of plant pollen proteins and more recently, have been identified as potential structural homologues of infectious agents of mammalian tissue, viral cell adhesion proteins and some plant disease resistance proteins. The questions that the laboratory is currently addressing included the enzymatic mechanism of pectate lyases by structural, biochemical and genetic studies; identification and rational design of inhibitors by computer graphic methods; characterization of the parallel beta helix by CD and FTIR methods; the possible function of the unique parallel beta helix structural motif of pectate lyases in secretion or in pathogenic attack; and the functional relationship of pectate lyases to sequence and structural homologues.
   
Publications S.R. Herron, J.A. Benen, R.D. Scavetta, J. Visser and F. Jurnak. Structure and function of pectic enzymes: virulence factors of plant pathogens. Proc. Natl. Acad. Sci. U.S.A. 97,
8762-8769 (2000).
   
  S.E. Heffron and F. Jurnak. Structure of an EF-Tu complex with a thiazolyl peptide antibiotic determined at 2.35 Å resolution: atomic basis for GE2270A inhibition of EF-Tu. Biochemistry 39, 37-45 (2000).
   
  R.D. Scavetta, S.R. Herron, A.T. Hotchkiss, N. Kita, N.T. Keen, J.A. Benen, H.C. Kester, J. Visser and F. Jurnak. Structure of a plant cell wall fragment complexed to pectate lyase C. Plant Cell 11, 1081-1092 (1999).
   
  J. Vitali, B. Schick, H. Kester, J. Visser and F. Jurnak.
The three-dimensional structure of an Aspergillus niger pectinlyase B at 1.7 Å resolution. Plant Physiol.116, 69-80 (1998).
   
  S.E. Lietzke, R.D. Scavetta, M.D. Yoder and F. Jurnak. The
refined three-dimensional structure of pectate lyase E from
Erwinia Chrysanthemi at 2.2 Å resolution. Plant Physiol. 111, 73-92 (1996).
   
  F. Jurnak, N. Kita, M. Garrett, S.E. Heffron, R. Scavetta,
C.M. Boyd and N.T. Keen. Functional implications of the
three-dimensional structures of pectate lyases. In,
Pectin and Pectinases, Progress in Biotechnology,
J. Visser and A.G.J. Voragen, Eds. Elsevier Science,
Amsterdam, Vol. 14, pp. 295-308 (1996).
   
  K. Abel and F. Jurnak. A complex profile of protein
elongation - translating chemical energy into molecular
movement. Structure 4, 229-238 (1996).
   
  B. Schick and F. Jurnak. Extension of the diffraction
resolution of crystals. Acta Cryst. D 50, 563-568 (1994).
   
  M.D. Yoder, N.T. Keen and F. Jurnak. New domain motif - the
structure of pectate lyase C, a secreted plant virulence
factor. Science 260, 1503-1507 (1993).
   
Graduate Programs Structural Biology and Molecular Biophysics

   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=3271
   
Last updated 03/12/2002