Faculty

Louis Noodleman 
Associate Professor of Molecular Biology
Department of Molecular Biology
TSRI - 1988

Education 
Ph.D., Massachusetts Institute of Technology, 1975

Awards & Activities 
Editorial Advisory Board, Journal of Biological Inorganic Chemistry, 2000 - 2002

Research Focus 
Electronic Structure and Reactions of Iron-Sulfur Electron Transfer Proteins and Redox Enzymes, and for Iron-Oxo Enzymes

We use modern methods of quantum chemistry (density functional methods) and protein electrostatics to investigate electronic structures, spectroscopy and the reaction pathways for the active sites of redox metalloproteins. (1) Iron-sulfur proteins are electron transfer agents in the electron transport chains of respiration, photosynthesis, and for metabolic conversions. (2) The enzyme nitrogenase is a complicated multielectron redox catalyst for the conversion of molecular nitrogen to ammonia, forming a primary building block for making amino and nucleic acids.

We are investigating electron and proton transfer into the active iron-molybdenum cofactor active site, and the subsequent reaction pathway. (3) We are studying the mechanisms of the iron-oxo dimer enzymes methane monooxygenase (MMO) and ribonucleotide reductase (RNR). Using two electron redox and oxygen activation chemistry, MMO hydroxylates hydrocarbons while RNR produces a tyrosine radical which by a long range radical propagation and H abstraction generates deoxyribonucleotides from ribonucleotides, the first step in DNA synthesis. These are chemically difficult and biologically important reactions. Common themes include the coupling between electron and proton transfer, the modulation of redox potentials by the active site cluster and the protein and solvent environment, and the activation of small molecule substrates, including molecular nitrogen or oxygen.

Selected References 
Noodleman, L., Lovell, T., Liu, T., Himo, F., Torres, R.A. Insights into properties and energetics of iron-sulfur proteins from simple clusters to nitrogenase. Curr. Opinion Chem. Biology 6:259, 2002.

Lovell, T., Li, J., Liu, T., Case, D.A., Noodleman, L. MoFe Cofactor of Nitrogenase: A density functional study of states M (N), M (OX) ,M (R), and M (I). J. Am. Chem. Soc. 123:12392, 2001.

Lovell, T., Li, J., Noodleman, L. Density functional studies of oxidized and reduced methane monooxygenase. Optimized geometries and exchange coupling of active site clusters. Inorg. Chem. 40, 5251-5266, 2001.

Lovell, T., Li, J., Noodleman, L. Energetics of oxidized and reduced methane monooxygenase active site clusters in the protein environment. Inorg. Chem. 40, 5267-5278, 2001.