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Structural Enzymology

Enzymes play central roles in all metabolic and cellular signaling pathways. Many investigators in the department are interested in understanding how enzymes function at the molecular and atomic level through a combination of modern biochemistry and structural biology. Techniques which are being employed to investigate enzyme structure and dynamics include X-ray crystallography, NMR, mass spectroscopy and protein chemistry, while their chemical behavior is being characterized by rapid-reaction and steady-state kinetics, calorimetry, chemical analyses, and a variety of spectroscopies. Protein engineering is being used to study how structure determines function. Through the use of these techniques, investigators are able to probe mechanism and specificity in order to gain a greater understanding of how enzymes work and how they function in the context of molecular pathways in the cell. Such knowledge could provide the basis for new medical treatments, pollution-control strategies, or many other applications.

David Ballou, Ph.D.

Mechanisms of biological redox reactions and reactions with oxygen, especially metalloproteins and flavoproteins; physical and chemical studies, including rapid reaction techniques and instrumentation development. More

Ruma V. Banerjee, Ph.D.

Structure and mechanisms of radical and redox-active enzymes, the chemical biology of B12 trafficking, regulation of human sulfur metabolism, biochemistry of B-vitamin associated human metabolic diseases, redox communication between glial, neural, dendritic and T cells in immune and neuro-immune function. More

Carol A. Fierke, Ph.D.

RNA Processing. Protein Prenylation. Structure, Mechanism and Inhibition of metalloenzymes and ribozymes. Protein engineering of biosensors and biocatalysts. More

Robert S. Fuller, Ph.D.

Protein localization and vesicular transport in the eukaryotic secretory/endocytic pathways using budding yeast as a system and employing biochemical reconstitution, cell biology, genetics and fluorescence resonance energy transfer (FRET) microscopy as methods. Protein trafficking in human neurodegenerative and neurodevelopmental disease. Proteolytic processing by enzymes of the SPC/Kex2/furin family in yeast and metazoans with interest in structure-function relationships and discovery of human furin inhibitors as drug models for infectious, degenerative and neoplastic disease. More

Ari Gafni, Ph.D.

Studies of protein folding and interactions at the single molecule level; protein misfolding in human disease, specifically how the generation of toxic protein aggregates features in diabetes and Alzheimer's disease. More

Gary Glick, Ph.D.

Developing new methods to study the structure, folding, and dynamics of both DNA and RNA. Defining binding properties of anti-DNA autoantibodies that arise in the autoimmune disorder systemic lupus erythematosus. More

Ming Lei, Ph.D.

Structural and functional studies of the molecular mechanism of human telomere and its regulation with an emphasis in a multi-subunit complex (telosome) which forms the protective cap of the telomere. More

Neil Marsh, Ph.D.

Enzymology: Structure and mechanism of coenzyme B12 and S adenosylmethionine-dependent radical enzymes. Protein Design: synthesis of "Teflon" proteins - introducing new properties into proteins using fluorinated amino acids. More

Alex Ninfa, Ph.D.

Reconstitution of signal transduction systems from purified components, structure/function analysis of signal transduction enzymes, protein crystallography. Characterization of protein kinases, phosphatases, and nucleotide transferases involved in signal transduction. Organization of the gene cascade controlling nitrogen assimilation in bacteria. Development of synthetic systems that perform useful functions. More

Patrick J. O'Brien, Ph.D.

Biochemical, biophysical, and structural approaches to understanding mechanisms of human DNA repair. More

Bruce Palfey, Ph.D.

Mechanistic enzymology with a focus on flavoproteins involved in pyrimidine biosynthesis, tRNA maturation, inhibitor design, and structure/function relationships. More

Stephen W. Ragsdale, Ph.D.

Microbial metabolism of energy-relevant and greenhouse gases (CO, CO2, methane) and xenobiotics (e.g., PCBs); regulation by and metabolism of CO in humans; and the roles of metal ions in biology, including the mechanisms of nickel, B12 , heme, and iron-sulfur enzymes. We use transient and steady-state kinetics, spectroscopy, and molecular biology to uncover mechanistic information. More

Mark A. Saper, Ph.D.

The Saper lab studies the molecular mechanisms of how pathogenic bacteria produce and secrete a large capsule polysaccharide that enhances bacterial virulence. In particular, we focus on a regulatory tyrosine kinase and phosphatase in pathogenic E. coli. Techniques include enzyme kinetics and X-ray crystallography. More

Georgios Skiniotis, Ph.D.

Molecular electron microscopy of protein complexes; focusing on structural studies of chromatin modifiers and signaling cell surface receptors. More

Janet Smith, Ph.D.

Structure-function studies of proteins using X-ray crystallography with an emphasis on complex enzymes and the replication proteins of flaviviruses and alphaviruses. More

William L. Smith, Ph.D.

Nutritional biochemistry of omega-3 and omega-6 fatty acids. Lipid mediators particularly the prostaglandins. Biochemical pharmacology of cyclooxygenases that catalyze prostaglandin synthesis including the mechanisms by which cyclooxygenases are inhibited by aspirin, ibuprofen, COX-2 inhibitors and fish oil fatty acids. More

Raymond C. Trievel, Ph.D.

Chemical and structural biology of enzymes that covalently modify histones, transcription factors, and other nuclear proteins. Our current research focuses on elucidating the molecular mechanisms underlying the specificites of histone methyltransferases and demethylases and on developing new assays and reagents to characterize these enzymes. More

Matthew Young, Ph.D.

Regulatory mechanisms of the Cyclin Dependent Kinases and other protein kinases. Structural studies and computational modeling of molecular dynamics in signaling proteins. More

Robert Zand, Ph.D.

The research in my laboratory is directed at understanding the role of posttranslational modifications on a central nervous system protein present in the myelin membrane. This protein known as the myelin basic protein (MBP) is known to be extensively posttranslationally modified by phosphorylation, methylation, and deimination. More

Erik R. P. Zuiderweg, Ph.D.

Our lab works on finding inhibitors for the Hsp70 chaperones. Hsp70's have been implicated in cancer cell survival, and in protein folding diseases such as Alzheimer's and Parkinson's. Our lab uses NMR spectroscopy to elucidate the mechanism of the chaperones, and to find and characterize, in collaboration with the Jason Gestwicki lab, potential inhibitors. More