Linda Jen-Jacobson

  • Professor Emerita

Contact

Office: (412) 624-4969
Lab: (412) 624-4969
4249 Fifth Avenue
Pittsburgh, PA 15260

The long-range objective of our research is to gain insight into the molecular determinants for high DNA site selectivity by proteins. Our strategy uses the conceptual and analytical methods of biophysics and structural biochemistry in combination with the manipulation methods of synthetic chemistry and of molecular genetics, and emphasizes the concerted use of a number of tools. We are currently combining high resolution "structural perturbation" methods with isothermal titration calorimetry to obtain complete thermodynamic profiles (i.e., changes in enthalpy, entropy, heat capacity) for protein-DNA complex formation, together with computational modeling to complement our interpretations. Some of our current work focuses on the thermodynamic consequences of molecular strain, experimental measurement of solvation changes upon binding, and the molecular properties of mutant proteins with reduced specificity.

Our ongoing principal goal is to adduce general principles applicable to most or all sequence-specific DNA-binding proteins. Our work points to the importance of time-dependent (dynamic) characteristics of protein-DNA complexes, including binding-dependent conformational transitions in the proteins and DNA and configurational (conformational and vibrational) fluctuations in the protein-DNA complexes, so we are pursuing spectroscopic methods (Nuclear Magnetic Resonance and Electron Spin Resonance) that inform us about these dynamics. A profound understanding of these basic physicochemical principles and their applications is what we will ultimately need to develop methods for knowledge-based drug design and design of macromolecules to fulfill specific biological functions.

E-mail Lab

Sinha, K., S.S. Sangani, A. D.  Kehr, G. S

Sinha, K., S.S. Sangani, A. D.  Kehr, G. S Rule, *L. Jen-Jacobson (2016) Metal Ion Binding at the Catalytic Site Induces Widely Distributed Changes in a Sequence Specific Protein-DNA Complex. Biochemistry 55:6115–6132

Ghindilis, L., M. W. Smith, H. M. Simon, I. A.

Ghindilis, L., M. W. Smith, H. M. Simon, I. A. Seoudi, N. S. Yazvenko, I. A. Murray, X. Fu, K. Smith,  L. Jen-Jacobson, S-y. Xu  (2015) Restriction Cascade Exponential Amplification (RCEA) assay with an attomolar detection limit: a novel, highly specific, isothermal alternative to qPCR. Nature Scientific Reports  doi:10.1038/srep07737

Ji, M., L. Tan, L. Jen-Jacobson, S. Saxena, S.

Ji, M., L. Tan, L. Jen-Jacobson, S. Saxena, S. (2014) Insights into copper coordination in the EcoRI-DNA complex by ESR spectroscopy. Mol. Physics 112: 3173-3182

Sapienza, P.J., T. Niu, Kurpiewski, M. R., A. G

Sapienza, P.J., T. Niu, Kurpiewski, M. R., A. Grigorescu and L. Jen-Jacobson (2014) Thermodynamic and structural basis for relaxation of specificity in protein-DNA recognition.  J. Mol. Biol. http://dx.doi.org/10.1016/j.jmb.2013.09.005

Sinha,K., L. Jen-Jacobson and G. S. Rule (2013)

Sinha,K., L. Jen-Jacobson and G. S. Rule (2013) Divide and conquer is always best:  Sensitivity of methyl correlation experiments. J. Biomol. NMR 56:331-335

Ruthstein, S., M. Ji, P. Mehta, L. Jen-Jacobson

Ruthstein, S., M. Ji, P. Mehta, L. Jen-Jacobson and S. Saxena (2013) Sensitive Cu2+- Cu2+ distance measurements in a protein-DNA complex by double-quantum coherence. ESR J. Phys. Chem. B 117:6227-6230

Lin, H.K., S. F. Chase, T. M. Laue, L. Jen-Jaco

Lin, H.K., S. F. Chase, T. M. Laue, L. Jen-Jacobson* and M. A. Trakselis* (2012) Differential temperature-dependent multimeric assemblies of replication and repair polymerases on DNA increase processivity.  Biochemistry 51:7367-7382

Yang, Z., M. R. Kurpiewski, Ji, M., J. E. Towns

Yang, Z., M. R. Kurpiewski, Ji, M., J. E. Townsend,P. Mehta, L. Jen-Jacobson* and S. Saxena* (2012) ESR spectroscopy identifies inhibitory Cu2+ sites in a DNA-modifying enzyme to reveal determinants of catalytic specificity. PNAS 109:6366-6367; PNAS Plus: 109:E993-E1000.

Sarver, J. L., Townsend, J. E., Rajapakse, G., Jen

Sarver, J. L., Townsend, J. E., Rajapakse, G., Jen-Jacobson, L. and Saxena, S. (2012) Simulating the dynamics and orientations of spin-labeled side chains in a protein-DNA complex. J. Phys. Chem. B. 116:4024-4033

Sinha, K., L. Jen-Jacobson and G.S. Rule (2011) Specific labeling of threonine methyl groups for

Sinha, K., L. Jen-Jacobson and G.S. Rule (2011) Specific labeling of threonine methyl groups for NMR studies of protein-nucleic acid complexes. Biochemistry 50:10189-10191.

Hancock, S.P., D.A. Hiller, J.J. Perona, and L. Jen-Jacobson (2011) The energetic contribution of

Hancock, S.P., D.A. Hiller, J.J. Perona, and L. Jen-Jacobson (2011) The energetic contribution of induced electrostatic asymmetry to DNA bending by a site-specific protein. J. Mol. Biol. 406:285-312 (PDF Reprint: 1.6 MB)

Dylla-Spears, R., J.E. Townsend, L. Jen-Jacobson, L.L. Sohn, and S.J. Muller (2010) Single-molecu

Dylla-Spears, R., J.E. Townsend, L. Jen-Jacobson, L.L. Sohn, and S.J. Muller (2010) Single-molecule sequence detection via microfluidic planar extensional flow at a stagnation point. Lab Chip 10:1543-1549 (PDF Reprint: 1.9 MB)

Mikheikin, A.L., H.K. Lin, P. Mehta, L. Jen-Jacobson, and M.A. Trakselis (2009) A trimeric DNA po

Mikheikin, A.L., H.K. Lin, P. Mehta, L. Jen-Jacobson, and M.A. Trakselis (2009) A trimeric DNA polymerase complex increases the native replication processivity. Nucleic Acids Res. 37:7194-7205 (PDF Reprint: 9.9 MB)

Dylla-Spears, R., J.E. Townsend, L.L. Sohn, L. Jen-Jacobson, and S.J. Muller (2009) Fluorescent M

Dylla-Spears, R., J.E. Townsend, L.L. Sohn, L. Jen-Jacobson, and S.J. Muller (2009) Fluorescent Marker for Direct Detection of Specific dsDNA Sequences. Anal. Chem. 81:10049-10054 (PDF Reprint: 2.8 MB)

VanderVeen, L.A., T.M. Harris, L. Jen-Jacobson, and L.J. Marnett (2008) Formation of DNA-protein

VanderVeen, L.A., T.M. Harris, L. Jen-Jacobson, and L.J. Marnett (2008) Formation of DNA-protein cross-links between gamma-hydroxypropanodeoxyguanosine and EcoRI. Chem. Res. Toxicol. 21:1733-1738 (PDF Reprint: 2.8 MB)

Stone, K.M., J.E. Townsend, J. Sarver, P.J. Sapienza, S. Saxena, and L. Jen-Jacobson (2008) Elect

Stone, K.M., J.E. Townsend, J. Sarver, P.J. Sapienza, S. Saxena, and L. Jen-Jacobson (2008) Electron spin resonance shows common structural features for different classes of EcoRI-DNA complexes. Angew. Chem. Int. Ed. Engl. 47:10192-10194 (PDF Reprint: 784 kb)

Jen-Jacobson, L., and L.A. Jacobson (2008) The role of water and the effects of small ions in sit

Jen-Jacobson, L., and L.A. Jacobson (2008) The role of water and the effects of small ions in site-specific protein-DNA interactions. Pp in Structural Biology of Protein-Nucleic Acid Interactions, Rice, P.A., and C. Correll, Ed. Royal Society of Chemistry Publishing, Cambridge

Sapienza, P.J., J.M. Rosenberg, and L. Jen-Jacobson (2007) Structural and thermodynamic basis for

Sapienza, P.J., J.M. Rosenberg, and L. Jen-Jacobson (2007) Structural and thermodynamic basis for enhanced DNA binding by a promiscuous mutant EcoRI endonuclease. Structure 15:1368-1382 (PDF Reprint: 2.6 MB)

Sapienza, P.J., C.A. Dela Torre, W.H. .4.t. McCoy, S.V. Jana, and L. Jen-Jacobson (2005) Thermody

Sapienza, P.J., C.A. Dela Torre, W.H. .4.t. McCoy, S.V. Jana, and L. Jen-Jacobson (2005) Thermodynamic and kinetic basis for the relaxed DNA sequence specificity of "promiscuous" mutant EcoRI endonucleases. J. Mol. Biol. 348:307-324 (PDF Reprint: 575 kb)

Kurpiewski, M.R., L.E. Engler, L.A. Wozniak, A. Kobylanska, M. Koziolkiewicz, W.J. Stec, and L. J

Kurpiewski, M.R., L.E. Engler, L.A. Wozniak, A. Kobylanska, M. Koziolkiewicz, W.J. Stec, and L. Jen-Jacobson (2004) Mechanisms of coupling between DNA recognition specificity and catalysis in EcoRI endonuclease. Structure 12:1775-1788 (PDF Reprint: 363 kb)

Shuttleworth, G., M.J. Fogg, M.P. Kurpiewski, L. Jen-Jacobson, and B.A. Connolly (2004) Recogniti

Shuttleworth, G., M.J. Fogg, M.P. Kurpiewski, L. Jen-Jacobson, and B.A. Connolly (2004) Recognition of the pro-mutagenic base uracil by family B DNApolymerases from Archaea. J. Mol. Biol. 337:621-634 (PDF Reprint: 2.0 MB)

Engler, L.E., P. Sapienza, L.F. Dorner, R. Kucera, I. Schildkraut, and L. Jen-Jacobson (2001) The

Engler, L.E., P. Sapienza, L.F. Dorner, R. Kucera, I. Schildkraut, and L. Jen-Jacobson (2001) The energetics of the interaction of BamHI endonuclease with its recognition site GGATCC. J. Mol. Biol. 307:619-636 (PDF Reprint: 1.7 MB)

Connolly, B.A., H.H. Liu, D. Parry, L.E. Engler, M.R. Kurpiewski, and L. Jen-Jacobson (2001) Assa

Connolly, B.A., H.H. Liu, D. Parry, L.E. Engler, M.R. Kurpiewski, and L. Jen-Jacobson (2001) Assay of restriction endonucleases using oligonucleotides. Methods Mol. Biol. 148:465-490

Watrob, H., W. Liu, Y. Chen, S.G. Bartlett, L. Jen-Jacobson, and M.D. Barkley (2001) Solution con

Watrob, H., W. Liu, Y. Chen, S.G. Bartlett, L. Jen-Jacobson, and M.D. Barkley (2001) Solution conformation of EcoRI restriction endonuclease changes upon binding of cognate DNA and Mg2+ cofactor. Biochemistry 23:683-692

Jen-Jacobson, L., L. E. Engler, and L. A. Jacob

Jen-Jacobson, L., L. E. Engler, and L. A. Jacobson (2000) "Structural and Thermodynamic strategies for site-specific DNA binding proteins.  Structure  8:1015-1023        

Jen-Jacobson, L., L.E. Engler, J.T. Ames, M.R. Kurpiewski, and A. Grigorescu (2000) Thermodynamic

Jen-Jacobson, L., L.E. Engler, J.T. Ames, M.R. Kurpiewski, and A. Grigorescu (2000) Thermodynamic parameters of specific and nonspecific protein-DNA binding. Supramol. Chem. 12:143-160 (PDF Reprint: 1.6 MB)
Dr. Jen-Jacobson received her Ph.D. (Biochemistry) in 1967 from the University of Illinois, and joined the Department in 1975.

Elected AAAS Fellow, 2001

NIH MERIT Award 2001-11

Chancellor's Distinguish Research Award, 2001