Anthony K. Mittermaier

Learn More
Protein structure is inherently dynamic, with function often predicated on excursions from low to higher energy conformations. For example, X-ray studies of a cavity mutant of T4 lysozyme, L99A, show that the cavity is sterically inaccessible to ligand, yet the protein is able to bind substituted benzenes rapidly. We have used novel relaxation dispersion(More)
There is growing evidence that structural flexibility plays a central role in the function of protein molecules. Many of the experimental data come from nuclear magnetic resonance (NMR) spectroscopy, a technique that allows internal motions to be probed with exquisite time and spatial resolution. Recent methodological advancements in NMR have extended our(More)
NMR Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments represent a powerful approach for characterizing protein internal motions and for gaining insight into fundamental biological processes such as protein folding, catalysis, and allostery. In most cases, CPMG data are analyzed assuming that the protein exchanges between two different(More)
Biological macromolecules are highly flexible and continually undergo conformational fluctuations on a broad spectrum of timescales. It has long been recognized that dynamics have an important role in the action of these molecules. However, the relationship between molecular function and motion is extremely challenging to delineate, because the(More)
Low solubility is a major stumbling block in the detailed structural and functional characterization of many proteins and isolated protein domains. The production of some proteins in a soluble form may only be possible through alteration of their sequences by mutagenesis. The feasibility of this approach has been demonstrated in a number of cases where(More)
Recently developed carbon transverse relaxation dispersion experiments (Skrynnikov, N. R.; et al. J. Am. Chem. Soc. 2001, 123, 4556-4566) were applied to the study of millisecond to microsecond time scale motions in a cavity mutant of T4 lysozyme (L99A) using methyl groups as probes of dynamics. Protein expressed in E. coli cells with (13)CH(3)-pyruvate as(More)
The three-site exchange folding reaction of an (15)N-labeled, highly deuterated Gly48Met mutant of the Fyn SH3 domain has been characterized at 25 degrees C using a suite of six CPMG-type relaxation dispersion experiments that measure exchange contributions to backbone (1)H and (15)N transverse relaxation rates in proteins. It is shown that this suite of(More)
The ribonucleoprotein (RNP) domain is one of the most common eukaryotic protein domains, and is found in many proteins involved in recognition of a wide variety of RNAs. Two structures of RNA complexes of human U1A protein have revealed important aspects of RNP-RNA recognition, but have also raised intriguing questions concerning how RNP domains(More)
Allostery has been studied for many decades, yet it remains challenging to determine experimentally how it occurs at a molecular level. We have developed an approach combining isothermal titration calorimetry, circular dichroism and nuclear magnetic resonance spectroscopy to quantify allostery in terms of protein thermodynamics, structure and dynamics. This(More)
Side-chain 2H NMR relaxation data have been collected for the SH3 domain from the Fyn tyrosine kinase and analyzed with respect to sequence preference and per-residue solvent accessibility. Residues that are highly preferred at a given position show a tendency to be less mobile than average with a coefficient of correlation that is greater than that(More)