Macromolecular Structure and Mechanism

Many investigators in the department focus on how biological macromolecules function at the molecular and atomic level through a combination of modern biochemistry and structural biology. Techniques that are being employed to investigate structure and dynamics of macromolecules include X-ray crystallography, cryo-electron microscopy, NMR, mass spectrometry, and single-molecule studies, while their chemical behavior is being characterized by rapid-reaction and steady-state kinetics, calorimetry, chemical analyses, and a variety of spectroscopies. Proteins and nucleic acids are also being engineered to study how macromolecular structure determines function. These experimental approaches enable investigators to probe mechanism and specificity in order to gain a greater understanding of how macromolecules 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.

Primary Faculty

Ruma Banerjee, Ph.D.

Chemical biology of hydrogen sulfide signaling; regulation of mammalian sulfur metabolism in health and disease; structural enzymology of human B12 trafficking proteins

Uhn-Soo Cho, Ph.D.

Biochemical and structural studies of kinetochore assembly, histone chaperones, and Sestrin-mediated mTORC1 regulation

Michael Cianfrocco, Ph.D.

Structural biology and biophysics underlying microtubule-based intracellular transport

Peter Freddolino, Ph.D.

High throughput structure-based function prediction, optimal use of cross-linking mass spectrometry for structure determination, structural genomics

Robert Fuller, Ph.D.

Protein localization and processing in the eukaryotic secretory pathway

James Morrissey, Ph.D.

Biochemistry of the human blood clotting system; structural studies of protein-membrane complexes

Patrick O'Brien, Ph.D.

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

Bruce Palfey, Ph.D.

Enzyme reaction mechanisms and inhibitor design, with a focus on therapeutically important flavoproteins

Stephen Ragsdale, Ph.D.

Molecular mechanisms of enzymes involved in metabolism of energy-relevant and greenhouse gases (CO, CO₂, methane), heme, and methylmercury; mechanisms of nickel, B12, heme, and iron-sulfur enzymes

Mark Saper, Ph.D.

Structural studies of bacterial cell wall endopeptidases (“autolysins”) to understand how they are regulated during cell growth and division

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

Raymond Trievel, Ph.D.

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

Zhaohui Xu, Ph.D.

Structural biology and molecular mechanisms of protein folding and trafficking in eukaryotic cells

Secondary Joint Faculty

Yali Dou, Ph.D.

Functions of chromatin modification enzymes in transcription regulation, cell fate determination, and cancer

Neil Marsh, Ph.D.

Structure and mechanism of radical S-adenosylmethionine-dependent enzymes, enzymes in hydrocarbon biosynthesis and degradation, design of self-assembling protein nano-cages

Nils Walter, Ph.D.

Powerful single molecule studies of mechanistic structure-dynamics-function relationships in RNAs of biomedical and bioanalytical significance; current work ranges from small bacterial riboswitches to RNA-protein complexes involved in human disease