Kenneth A. Johnson

kajohnson@mail.utexas.edu
Biochemistry
Professor, Faculty
Roger J. Williams Centennial Professorship in Biochemistry
Kenneth A. Johnson

Contact Information

Office
MBB 3.122
Office Phone
471-0434
Fax
471-0435

Research Group

K. A. Johnson Lab

Education

BS, Chemistry, University of Iowa (1971);   PhD, Molecular Biology, University of Wisconsin (1975)

Mitochondrial DNA Polymerase and the Toxicity of Nucleoside Analogs used to treat AIDS

Several studies point to the likely role of the mitochondrial DNA polymerase in the toxicity of nucleoside analogs used in the treatment of viral infections such as hepatitis and AIDS. We have cloned the human mitochondrial DNA polymerase and have performed structural and kinetic studies to establish molecular basis for these dose-limiting toxic side effects. Our studies show that the toxicity is directly correlated with the kinetics of incorporation by the mitochondrial DNA polymerase. This work will enable us and others to develop less toxic nucleoside analogs.

HIV Reverse Transcriptase

Previously we have established the elementary steps leading to correct nucleotide incorporation by HIV reverse transcriptase, quantified the changes in individual kinetic constants occurring during misincorporation, determined the mechanism of action of a class of nonnucleoside inhibitors, and characterized changes leading to resistance against these agents. Currently we are continuing to explore the mechanisms of inhibition by nonnucleoside inhibitors and resistance to these drugs. A better understanding of these phenomena could lead to the development of better combination therapies in the treatment of AIDS.

Microtubule-Dependent Motor ATPase

We have recently established the pathway of ATP hydrolysis by kinesin, a motor protein involved in fast axonal transport. In current work we are examining the kinetics and structure of kinesin to establish the mechanism of force production. The work serves as an important model for understanding energy transduction in general, and for exploring the family of kinesin-like ATPases which are responsible for a wide range of microtubule-dependent movements in all eukaryotic cells.

Kinetic Analysis of Macromolecules, edited by Kenneth A. Johnson is now available for sale. Paperback edition copies may be ordered from KinTek Corporation at a cost of $70.00 each. For additional information, see the Oxford University Press Practical Approach series.

The 2005 3rd Annual "Dawn of the New Enzymology" Kinetics Workshop will be held January 9-12 in Austin, Texas, sponsored by KinTek Corporation. Dr. Johnson will provide an in-depth tutorial for those wanting to learn more about the logic and the power of transient kinetic methods. See http://www.kintek-corp.com for more information and registration forms.

Representative Publications

  • Lee, H., Hanes, J., and Johnson, K. A.  "Toxicity of Nucleoside Analogs Used to Treat AIDS and the Selectivity of the Mitochondrial DNA Polymerase (Review)" Biochemistry (2003)

  • Murakami, E., Feng J.Y., Lee, H, Hanes, J., Johnson, K.A., Anderson, K.S.  "Characterization of a novel reverse transcriptase and other RNA associated catalytic activities by human DNA polymerase gamma: Importance in mitochondrial DNA replication" J. Biol. Chem. 278 (2003): 36403-9.

  • Johnson, A.A., Ray, A. S., Hanes, J., Suo, Z., Colacino, J. M., Anderson, K. S., and Johnson, K. A.  " Toxicity of Antiviral Nucleoside Analogs and the Human Mitochondrial DNA Polymerase" J. Biol. Chem. 276 (2001): 40847-40857.

  • Johnson, A.A., and Johnson, K. A.  "Fidelity of Nucleotide Incorporation by Human Mitochondrial DNA Polymerase." J. Biol. Chem. 276 (2001): 38090-38096.

  • Johnson, A.A., and Johnson, K. A.  " Exonuclease proofreading by human mitochondrial DNA polymerase" J. Biol. Chem. 276 (2001): 38097-38107.