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Robert
Hausinger, Ph.D.
Professor
Department of Microbiology and Molecular Genetics
B.S.,
1977, University of Wisconsin
Ph.D., 1982, University
of Minnesota
Postdoctoral studies: 1982-1984, Massachusetts
Institute of Technology
Address:
Department of Microbiology and Molecular Genetics
6193 Biomedical Physical Sciences
Michigan State University
East Lansing, MI 48824
Email: hausinge@msu.edu
Telephone: (517) 355-6463 ext.1610 |
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Research
My
laboratory explores specific aspects of microbial physiology
and enzymology related to transition metals. In particular,
we study mechanisms of catalysis by metalloenzymes and
characterize the biosynthesis of protein metallocenters.
We use an array of experimental techniques and approaches
that ranges from gene cloning to enzyme kinetics, from
site-directed mutagenesis to metal ion binding assays,
and from active site peptide studies to biophysical
spectroscopic methods.
A
major emphasis in my laboratory focuses on characterization
of several ferrous ion and alpha-ketoglutarate dependent
hydroxylases. One of these enzymes, TfdA, catalyzes
the initial step in mineralization of the herbicide
2,4-D (2,4-dichlorophenoxyacetic acid). A second enzyme,
TauD, functions in bacterial metabolism of sulfonated
compounds. Finally, the most recent project centers
on AlkB, a unique DNA-repair enzyme that reverses alkylation
damage. Current work with these enzymes includes metallocenter
analysis by spectroscopic methods, characterization
of site-directed mutant proteins and examination of
alternate substrates and inhibitors.
A
second area of emphasis in the laboratory centers on
the mechanism of activation for the nickel-dependent
enzyme urease. Bacterial urease is associated with the
formation of urinary deposits (kidney stones) during
human infection, and uncontrolled hydrolysis of urea
based fertilizers can lead to crop damage; thus, a detailed
understanding of urease activation may allow the design
of pharmacologically or agriculturally effective inhibitors
of this enzyme. Within the urease gene cluster are seven
genes: three genes encode the three urease subunits
(of known 3D structure), and four genes encode "accessory
proteins". One of the accessory proteins is a "metallochaperone"
that delivers nickel ion; we now know the structure
of this protein. The other three accessory proteins
work together to form a complex with urease apoprotein.
We are presently examining the role of each of these
components in the mechanism of nickel incorporation
into urease.
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