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Ann M. Valentine

Assistant Professor, Inorganic & Biophysical Chemistry
E-mail: ann.valentine@yale.edu
Web site: http://xbeams.chem.yale.edu/~valentine

Biographical Sketch

B.S. University of Virginia, 1993
Ph.D. MIT, 1998
Postdoc Penn State University, 1998-2001
Joined Yale faculty 2001
Research Corporation Research Innovation Award, 2003
NSF CAREER Award, 2004

Research Description

Bioinorganic chemistry, the study of the molecular transactions of inorganic elements in biological systems, is the focus of our research. This field may encompass investigations of biomolecules that naturally contain inorganic elements (such as iron in hemoglobin) or toxic effects of some metals in the body (as in lead or mercury poisoning). Inorganic compounds can be used as probes of natural systems (in technetium-based imaging agents) or as drugs to combat disease (such as the anti-cancer drug cisplatin). Spectroscopic methods have become more sensitive and better synthetic model compounds are available for comparison to natural systems. At the same time, biochemistry and molecular biology have undergone what can only be called a revolution in recent years, with the techniques of genetic manipulation and genomics making possible experiments that were once unimaginable. Bioinorganic chemistry is able to take full advantage of all of these developments, as well as advances in structural biology and computational chemistry. This interdisciplinary and very collaborative field teaches a broad background to its students. A researcher will have knowledge of inorganic chemistry, the properties of metals, and the capabilities, requirements, and limitations of spectroscopy. In addition, cognizance of biochemistry is required, so that the researcher retains a sense of how a given biomolecule fits into a biochemical pathway and the chemistry of a cell. Facility with biochemical techniques is also vital.

The Valentine lab follows a problem-based approach to bioinorganic chemistry and will use whatever methods and approaches afford the most, and most important, information about problems of interest. Kinetics, spectroscopy, mutagenesis, and other methods will complement each other. Some specific areas of investigation are:

• The post-synthetic modification of newly synthesized aromatic polyketide antibiotics by metalloenzymes.
• Synthesis, characterization, and evaluation of potential titanium-based anticancer drugs.
• The sequestration and use of metals by marine organisms.
• Metal transport by primitive plasma proteins.

Selected References

• Valentine, A. M. “Titanium: Inorganic and Coordination Chemistry” in Encyclopedia of Inorganic Chemistry, 2^nd ed., R.B. King, ed. Chichester: John Wiley and Sons, 2004.
• Trakselis, M. A., Roccasecca, R. M., Yang J., Valentine A. M., Benkovic S. J. “Dissociative Properties of the Proteins Within the Bacteriophage T4 Replisome” J. Biol. Chem., 2003, 278, 49839 - 49849.
• Valentine, A. M.; Ishmael, F. T.; Shier, V. K.; Benkovic, S. J. “A Zinc Ribbon Protein in DNA Replication: Primer Synthesis and Macromolecular Interactions by the Bacteriophage T4 Primase” Biochemistry, 2001, 40, 15074-15085.
• Wang, Z.; Fast W.; Valentine, A. M.; Benkovic, S. J. “Metallo-beta-lactamase: structure and mechanism” Curr. Opin. Chem. Biol. 1999, 3, 614-622.
• Valentine, A. M.; Stahl, S. S.; Lippard, S. J. “Mechanistic Studies of the Reaction of Reduced Methane Monooxygenase Hydroxylase with Dioxygen and Substrates” J. Am. Chem. Soc., 1999, 121, 3876-3887.

Last modified: July 10, 2005 (kp)