The Drennan laboratory uses X-ray crystallography as the chief tool for investigating the structure and function of enzymes that are medically important or valuable in environmental remediation. We are particularly interested in metalloprotein biochemistry and in the role of conformational change in catalysis. Representative projects are described below.

Metalloenzymes & Medicine
Ribonucleotide reductases (RNRs) catalyze an essential step in DNA biosynthesis, the conversion of ribonucleotides to deoxyribonucleotides. RNR inhibition reduces cellular pools of deoxynucleoside triphosphates (dNTPs) and consequently impairs DNA biosynthesis and repair. As a result of these activities, RNRs are being pursued as targets for antiviral and antitumor therapies. To provide a molecular understanding of the catalytic and allosteric regulatory enzyme mechanisms, we are carrying out crystallographic studies of the simplest members of the RNR family (class II RNRs).

Metalloenzymes & the Environment
Carbon monoxide dehydrogenases (CODHs) play an important role in reducing levels of toxic CO gas in our environment. An estimated 108 tons of CO are removed annually from the earth and lower atmosphere by bacteria. A better understanding of the structure and mechanism of Ni-Fe-S-dependent carbon monoxide dehydrogenases could lead to development of biomimetic catalysts to lower CO levels in heavily polluted regions.