Geoffrey A. Mueller, W. Y. Choy, Daiwen Yang, Julie D. Forman, Ronald A. Venters, Lewis E. Kay, ...
Recent methodological developments in solution state NMR spectroscopy of proteins have dramatically reduced the size limitations that have traditionally prohibited detailed NMR studies of
Center of Excellence and Departments of Medical (2008)
Oscar Millet, Anthony Mittermaier, David Baker, Lewis E. Kay, Genetics Biochemistry
The structural and dynamic properties of proteins are determined by their primary amino acid sequence. Elucidation of the rules that govern this relationship is of immense practical and
Zarrine-Afsar, Arash, Mittermaier, Anthony, Kay, Lewis E., Davidson, Alan R.
Guanidinium hydrochloride (GuHCl) at low concentrations significantly stabilizes the Fyn SH3 domain. In this work, we have demonstrated that this stabilizing effect is manifested through a dramatic...
Mittermaier, Anthony, Kay, Lewis E.
We have used 15N- and 2H-NMR spin relaxation experiments to study the response of backbone and side-chain dynamics when a leucine or valine is substituted for a completely buried phenylalanine...
A Magnetic Resonance Realization of Decoherence-Free Quantum Computation (2003)
Ollerenshaw, Jason E., Lidar, Daniel A., Kay, Lewis E.
We report the realization, using nuclear magnetic resonance techniques, of the first quantum computer that reliably executes an algorithm in the presence of strong decoherence. The computer is based...
Li, Shun-Cheng, Songyang, Zhou, Vincent, Sébastien J. F., Zwahlen, Catherine, Wiley, Sandra, Cantley, Lewis, ...
The phosphotyrosine-binding (PTB) domain is a recently identified protein module that has been characterized as binding to phosphopeptides containing an NPXpY motif (X = any amino acid). We describe...
Hwang, Peter M., Li, Chengjun, Morra, Massimo, Lillywhite, Jennifer, Muhandiram, D.Ranjith, Gertler, Frank, ...
The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent...
Solution structure and dynamics of the outer membrane enzyme PagP by NMR
Hwang, Peter M., Choy, Wing-Yiu, Lo, Eileen I., Chen, Lu, Forman-Kay, Julie D., Raetz, Christian R. H., ...
The bacterial outer membrane enzyme PagP transfers a palmitate chain from a phospholipid to lipid A. In a number of pathogenic Gram-negative bacteria, PagP confers resistance to certain cationic...
Donaldson, Logan W., Gish, Gerald, Pawson, Tony, Kay, Lewis E., Forman-Kay, Julie D.
On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221...
Millet, Oscar, Hudson, Rhea P., Kay, Lewis E.
Maltose-binding protein (MBP) is a two-domain protein that undergoes a ligand-mediated conformational rearrangement from an “open” to a “closed” structure on binding to maltooligosaccharides....
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb
Zwahlen, Catherine, Li, Shun-Cheng, Kay, Lewis E., Pawson, Tony, Forman-Kay, Julie D.
The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in...
Dramatic acceleration of protein folding by stabilization of a nonnative backbone conformation
Di Nardo, Ariel A., Korzhnev, Dmitry M., Stogios, Peter J., Zarrine-Afsar, Arash, Kay, Lewis E., Davidson, Alan R.
Through a mutagenic investigation of Gly-48, a highly conserved position in the Src homology 3 domain, we have discovered a series of amino acid substitutions that are highly destabilizing, yet...
The integral membrane enzyme PagP alternates between two dynamically distinct states
Hwang, Peter M., Bishop, Russell E., Kay, Lewis E.
PhoPQ-activated gene P (PagP) is an integral membrane enzyme that transfers the sn-1 palmitate chain from phospholipid to lipopolysaccharide in Gram-negative bacteria. A recent x-ray crystallographic...
A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin
Ahn, Victoria E, Lo, Eileen I, Engel, Christian K, Chen, Lu, Hwang, Peter M, Kay, Lewis E, ...
The ability of enzymes to distinguish between fatty acyl groups can involve molecular measuring devices termed hydrocarbon rulers, but the molecular basis for acyl-chain recognition in any...
Ollerenshaw, Jason E., Kaya, Hüseyin, Chan, Hue Sun, Kay, Lewis E.
A complete description of how a protein folds requires the characterization of intermediate conformations traversed during the folding transition. We have calculated dynamics trajectories of a...
Solution NMR-derived global fold of a monomeric 82-kDa enzyme
Tugarinov, Vitali, Choy, Wing-Yiu, Orekhov, Vladislav Yu., Kay, Lewis E.
The size of proteins that can be studied by solution NMR spectroscopy has increased significantly because of recent developments in methodology. Important experiments include those that make use of...
Site-specific contributions to the pH dependence of protein stability
Tollinger, Martin, Crowhurst, Karin A., Kay, Lewis E., Forman-Kay, Julie D.
Understanding protein stability is a significant challenge requiring characterization of interactions within both folded and unfolded states. Of these, electrostatic interactions influence ionization...
Sprangers, Remco, Gribun, Anna, Hwang, Peter M., Houry, Walid A., Kay, Lewis E.
The highly conserved, 300-kDa cylindrical protease ClpP is an important component of the cellular protein quality machinery. It consists of 14 subunits arranged into two heptameric rings that enclose...
Li, Shun-Cheng, Songyang, Zhou, Vincent, Sébastien J. F., Zwahlen, Catherine, Wiley, Sandra, Cantley, Lewis, ...
The phosphotyrosine-binding (PTB) domain is a recently identified protein module that has been characterized as binding to phosphopeptides containing an NPXpY motif (X = any amino acid). We describe...
Hwang, Peter M., Li, Chengjun, Morra, Massimo, Lillywhite, Jennifer, Muhandiram, D.Ranjith, Gertler, Frank, ...
The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent...
Solution structure and dynamics of the outer membrane enzyme PagP by NMR
Hwang, Peter M., Choy, Wing-Yiu, Lo, Eileen I., Chen, Lu, Forman-Kay, Julie D., Raetz, Christian R. H., ...
The bacterial outer membrane enzyme PagP transfers a palmitate chain from a phospholipid to lipid A. In a number of pathogenic Gram-negative bacteria, PagP confers resistance to certain cationic...
Donaldson, Logan W., Gish, Gerald, Pawson, Tony, Kay, Lewis E., Forman-Kay, Julie D.
On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221...
Millet, Oscar, Hudson, Rhea P., Kay, Lewis E.
Maltose-binding protein (MBP) is a two-domain protein that undergoes a ligand-mediated conformational rearrangement from an “open” to a “closed” structure on binding to maltooligosaccharides....
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb
Zwahlen, Catherine, Li, Shun-Cheng, Kay, Lewis E., Pawson, Tony, Forman-Kay, Julie D.
The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in...
Site-specific contributions to the pH dependence of protein stability
Tollinger, Martin, Crowhurst, Karin A., Kay, Lewis E., Forman-Kay, Julie D.
Understanding protein stability is a significant challenge requiring characterization of interactions within both folded and unfolded states. Of these, electrostatic interactions influence ionization...
Dramatic acceleration of protein folding by stabilization of a nonnative backbone conformation
Di Nardo, Ariel A., Korzhnev, Dmitry M., Stogios, Peter J., Zarrine-Afsar, Arash, Kay, Lewis E., Davidson, Alan R.
Through a mutagenic investigation of Gly-48, a highly conserved position in the Src homology 3 domain, we have discovered a series of amino acid substitutions that are highly destabilizing, yet...
The integral membrane enzyme PagP alternates between two dynamically distinct states
Hwang, Peter M., Bishop, Russell E., Kay, Lewis E.
PhoPQ-activated gene P (PagP) is an integral membrane enzyme that transfers the sn-1 palmitate chain from phospholipid to lipopolysaccharide in Gram-negative bacteria. A recent x-ray crystallographic...
A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin
Ahn, Victoria E, Lo, Eileen I, Engel, Christian K, Chen, Lu, Hwang, Peter M, Kay, Lewis E, ...
The ability of enzymes to distinguish between fatty acyl groups can involve molecular measuring devices termed hydrocarbon rulers, but the molecular basis for acyl-chain recognition in any...
Ollerenshaw, Jason E., Kaya, Hüseyin, Chan, Hue Sun, Kay, Lewis E.
A complete description of how a protein folds requires the characterization of intermediate conformations traversed during the folding transition. We have calculated dynamics trajectories of a...
Solution NMR-derived global fold of a monomeric 82-kDa enzyme
Tugarinov, Vitali, Choy, Wing-Yiu, Orekhov, Vladislav Yu., Kay, Lewis E.
The size of proteins that can be studied by solution NMR spectroscopy has increased significantly because of recent developments in methodology. Important experiments include those that make use of...
Sprangers, Remco, Gribun, Anna, Hwang, Peter M., Houry, Walid A., Kay, Lewis E.
The highly conserved, 300-kDa cylindrical protease ClpP is an important component of the cellular protein quality machinery. It consists of 14 subunits arranged into two heptameric rings that enclose...
Vallurupalli, Pramodh, Kay, Lewis E.
Single-molecule fluorescence experiments have shown that the conformation of the complex between Escherichia coli general NAD(P)H:flavin oxidoreductase (FRE) and flavin adenine dinucleotide (FAD)...
Velyvis, Algirdas, Yang, Ying R., Schachman, Howard K., Kay, Lewis E.
The 306-kDa aspartate transcarbamoylase is a well studied regulatory enzyme, and it has emerged as a paradigm for understanding allostery and cooperative binding processes. Although there is a...
Murphy, James M., Korzhnev, Dmitry M., Ceccarelli, Derek F., Briant, Douglas J., Zarrine-Afsar, Arash, Sicheri, Frank, ...
The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is...
Zarrine-Afsar, Arash, Mittermaier, Anthony, Kay, Lewis E., Davidson, Alan R.
Guanidinium hydrochloride (GuHCl) at low concentrations significantly stabilizes the Fyn SH3 domain. In this work, we have demonstrated that this stabilizing effect is manifested through a dramatic...
Φ-Value analysis of a three-state protein folding pathway by NMR relaxation dispersion spectroscopy
Neudecker, Philipp, Zarrine-Afsar, Arash, Davidson, Alan R., Kay, Lewis E.
Experimental studies of protein folding frequently are consistent with two-state folding kinetics. However, recent NMR relaxation dispersion studies of several fast-folding mutants of the Fyn Src...
Mittermaier, Anthony, Kay, Lewis E.
We have used 15N- and 2H-NMR spin relaxation experiments to study the response of backbone and side-chain dynamics when a leucine or valine is substituted for a completely buried phenylalanine...
Measurement of bond vector orientations in invisible excited states of proteins
Vallurupalli, Pramodh, Hansen, D. Flemming, Stollar, Elliott, Meirovitch, Eva, Kay, Lewis E.
The focus of structural biology is on studies of the highly populated, ground states of biological molecules; states that are only sparsely and transiently populated are more difficult to probe...
Filippakopoulos, Panagis, Kofler, Michael, Hantschel, Oliver, Gish, Gerald D., Grebien, Florian, Salah, Eidarus, ...
The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved...
Structures of invisible, excited protein states by relaxation dispersion NMR spectroscopy
Vallurupalli, Pramodh, Hansen, D. Flemming, Kay, Lewis E.
Molecular function is often predicated on excursions between ground states and higher energy conformers that can play important roles in ligand binding, molecular recognition, enzyme catalysis, and...
Dynamic equilibrium engagement of a polyvalent ligand with a single-site receptor
Mittag, Tanja, Orlicky, Stephen, Choy, Wing-Yiu, Tang, Xiaojing, Lin, Hong, Sicheri, Frank, ...
Intrinsically disordered proteins play critical but often poorly understood roles in mediating protein interactions. The interactions of disordered proteins studied to date typically entail...