Dynamic personalities of proteins
- K. Henzler-Wildman, D. Kern
- BiologyNature
- 12 December 2007
The dream is to 'watch' proteins in action in real time at atomic resolution, which requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.
Two-state allosteric behavior in a single-domain signaling protein.
- B. Volkman, D. Lipson, D. Wemmer, D. Kern
- Biology, ChemistryScience
- 23 March 2001
A strong correlation is found between phosphorylation-driven activation of the signaling protein NtrC and microsecond time-scale backbone dynamics and a dynamic population shift between two preexisting conformations as the underlying mechanism of activation.
Intrinsic motions along an enzymatic reaction trajectory
- K. Henzler-Wildman, V. Thai, D. Kern
- Chemistry, BiologyNature
- 6 December 2007
The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to…
Enzyme Dynamics During Catalysis
- E. Eisenmesser, D. A. Bosco, M. Akke, D. Kern
- Chemistry, BiologyScience
- 22 February 2002
The rates of conformational dynamics of the enzyme strongly correlate with the microscopic rates of substrate turnover, which allow a prediction of the reaction trajectory.
A hierarchy of timescales in protein dynamics is linked to enzyme catalysis
- K. Henzler-Wildman, M. Lei, V. Thai, S. J. Kerns, M. Karplus, D. Kern
- BiologyNature
- 6 December 2007
It is shown that pico- to nano-second timescale atomic fluctuations in hinge regions of adenylate kinase facilitate the large-scale, slower lid motions that produce a catalytically competent state.
Intrinsic dynamics of an enzyme underlies catalysis
- E. Eisenmesser, Ó. Millet, D. Kern
- Chemistry, BiologyNature
- 3 November 2005
It is shown that the intrinsic plasticity of the protein is a key characteristic of catalysis, and the pre-existence of collective dynamics in enzymes before catalysis is a common feature of biocatalysts and that proteins have evolved under synergy pressure between structure and dynamics.
Hidden alternate structures of proline isomerase essential for catalysis
- J. Fraser, M. Clarkson, Sheena C. Degnan, R. Erion, D. Kern, T. Alber
- ChemistryNature
- 27 November 2009
Dual strategies of ambient-temperature X-ray crystallographic data collection and automated electron-density sampling are introduced to structurally unravel interconverting substates of the human proline isomerase, cyclophilin A (CYPA).
Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A
- D. A. Bosco, E. Eisenmesser, S. Pochapsky, W. Sundquist, D. Kern
- Chemistry, BiologyProceedings of the National Academy of Sciences…
- 2 April 2002
CypA does not only bind to CAN but also catalyzes efficiently the cis/trans isomerization of the Gly-89–Pro-90 peptide bond, providing experimental evidence for efficient CypA catalysis on a natively folded and biologically relevant protein substrate.
Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair
- M. Wolf-Watz, V. Thai, K. Henzler-Wildman, G. Hadjipavlou, E. Eisenmesser, D. Kern
- Biology, ChemistryNature Structural &Molecular Biology
- 29 August 2004
A comparative and quantitative study of activity, structure and dynamics revealed a close link between protein dynamics and catalytic turnover in hyperthermophilic and mesophilic homologs of adenylate kinase.
Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2
While autophosphorylation is the key regulatory mechanism in the centrosomes in the early stages of mitosis, allosteric activation by TPX2 of dephosphorylated Aurora A could be at play in the spindle microtubules.
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