Carlos Enrique Catalano,
Pharm.D., Ph.D.

Professor of Biochemistry

School of Pharmacy
Department of Pharmaceutical Sciences
University of Colorado at Denver and Health Sciences Center
Campus Box C238
4200 East Ninth Avenue
Denver, Colorado 80262

Office Phone: 303.315.8561
Lab Phone: 303.315.8562
Fax: 303.315.6281
carlos.catalano@uchsc.edu

EDUCATION/EXPERIENCE

HONORS

PROFESSIONAL ACTIVITIES

PERSONNEL

Research Interests: Mechanisms of Virus Assembly

Our laboratory is interested in the molecular mechanisms of genome packaging in the double-stranded DNA viruses. Similar mechanisms for genome packaging have been proposed for all of the dsDNA bacteriophages, and likely apply to mammalian viruses such as adenovirus and the herpesvirus groups. Terminase enzymes are common to all of these viruses and are responsible for the packaging of a single genome within the confines of a pre-formed, empty viral capsid.

We study the biochemical and biophysical properties of bacteriophage lambda terminase, and the nature of the multiple nucleoprotein complexes involved in the packaging process. Phage lambda terminase possesses a site-specific endonuclease activity, a DNA strand-separation activity, and a DNA-stimulated ATPase activity, all of which work in concert to effect genome packaging.

This enzyme is an integral part of several nucleoprotein intermediates that are required for successful packaging of the genome within the viral capsid. The experiments performed in our laboratory systematically probe the protein-protein and protein-DNA interactions required to assemble a stable nucleoprotein complex that site-specifically nicks a concatemeric DNA precursor, and the subsequent interactions required to disengage this complex from the assembly site so that packaging may ensue. The interplay between the three catalytic activities of lambda terminase in the assembly-release processes as well as communication between the ATPase catalytic sites is of interest.

We couple detailed enzyme kinetic analyses (steady-state and pre-steady-state) with biophysical characterization of protein-protein and protein-DNA interactions (CD spectroscopy, fluorescence spectroscopy, analytical ultracentrifugation, quantitative DNase footprinting, etc.) to characterize the structure and function of these nucleoprotein packaging complexes.

Efforts currently underway in our laboratory further seek to determine the three dimensional high-resolution structures of the terminase proteins. While mechanistic details may differ, the data derived from our studies may be used to model DNA packaging by other double-stranded DNA viruses, including assembly in the eucaryotic herpesvirus groups. A major effort will be directed towards isolation and characterization of the DNA packaging enzyme from herpesvirus, an enzyme functionally related to the phage terminases.

Selected Publications

• Yang Q., Catalano C.E. Biochemical characterization of bacteriophage lambda genome packaging in vitro. Virology 2003 Jan 20;305(2):276-87 [Abstract]

• de Beer T., Fang J., Ortega M., Yang Q., Maes L., Duffy C., Berton N., Sippy J., Overduin M., Feiss M., Catalano C.E. Insights into specific DNA recognition during the assembly of a viral genome packaging machine. Mol Cell. 2002 May;9(5):928-9 [Abstract]
  

• Bain, D.L., Berton, N., Ortega, M., Baran, J., Yang, Q., and Catalano, C.E. (2001) "Biophysical Characterization of the DNA Binding Domain of gpNu1, a Viral DNA Packaging Protein" J. Biol. Chem., 276(23), 20175-20181 [Abstract]

• Catalano, C.E. (2000) "The terminase enzyme from bacteriophage lambda: a DNA-packaging machine." Cellular and Molecular Life Sciences (formally Experientia), 57(1), 128-148. (Solicited Review) [Abstract]

• de Beer, T., Ortega, M., Berton, N., Yang, Q., Overduin, M., and Catalano, C.E. (2000) "Letter to the Editor: Assignment of the 1H, 13C, and 15N Resonances of the DNA Binding Domain of gpNu1, A Genome Packaging Protein from Bacteriophage Lambda" J. Biomolecular NMR, 18, 69-70 [no abstract]

• Yang, Q., Berton, N., c, M.C., and Catalano, C.E. (1999) "Domain Structure of gpNu1, a Phage Lambda DNA Packaging Protein" Biochemistry, 38: 14238-14247 [Abstract]

• Woods, L. and Catalano, C.E. (1999) "Kinetic Characterization of the GTPase Activity of Phage Lambda Termianse: Evidence for Communication Between the Two NTPase Catalytic Sites" Biochemistry, 38: 14624-14630 [Abstract]

• Yang, Q., de Beer, T., Woods, L., Meyer, J.D., Manning, M.C., Overduin, M., and Catalano, C.E. (1999) "Cloning, Expression, and Characterization of a DNA Binding Domain of gpNu1, a Phage Lambda DNA Packaging Protein" Biochemistry, 38:465-477 [Abstract]