The Role of Dynamics in Enzyme Activity

Daniel, Roy M.; Dunn, Rachel V.; Finney, John; Smith, Jeremy C.

doi:10.1146/annurev.biophys.32.110601.142445

Cited by 322 publications

(350 citation statements)

References 140 publications

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“…It has been shown that distributed mutations can contribute significantly to the tuning of pK a values. 40,44,45 Dynamic effects are known to play a role in enzyme catalysis [41][42][43]46 , although the precise effect and magnitude of their contributions remains controversial 2,3 . At the very least, an enzyme active site has to be deformable to maintain complementarity to the various species along the reaction coordinate [41][42][43] .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Local Encoding of Computationally Designed Enzyme Activity

Allert

Dwyer

Hellinga

2007

Journal of Molecular Biology

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One aim of computational protein design is to introduce novel enzyme activity into proteins of known structure by predicting mutations that stabilize transition states. Previously we have shown that it is possible to introduce triose phosphate isomerase activity into the ribose-binding protein of Escherichia coli by constructing 17 mutations in the first two layers of residues that surround the wild-type ligand-binding site. Here we report that these mutations can be "transplanted" into a homologous ribose-binding protein, isolated from the hyperthermophilic bacterium Thermoanaerobacter tengcongensis, with retention of catalytic activity, substrate affinity, and reaction pH dependence. The observed 10 5 -10 6 -fold rate enhancement corresponds to 70% of the maximally known transition-state binding energy. The wild-type sequences in these two homologues are almost perfectly conserved in the vicinity of their ribose-binding sites, but diverge significantly at increasing distance from these sites. The results demonstrate that the computationally designed mutations are sufficient to encode the observed enzyme activity, that all the observed activity is locally encoded within the layer of residues directly in contact with the substrate, and that in this case at least 70% of transition state stabilization energy can be achieved using straightforward considerations of stereochemical complementarity between enzyme and reactants.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Local Encoding of Computationally Designed Enzyme Activity

Allert

Dwyer

Hellinga

2007

Journal of Molecular Biology

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“…2000; Tarek & Tobias 2000Teeter et al 2001;Caliskan et al 2002;Paciaroni et al 2002). Highly viscous solvents, such as trehalose, suppress dynamical transition behaviour (Hagen et al 1995;Cordone et al 1999;Walser et al 2000), and neutron-scattering experiments on enzymes in a range of cryosolvents showed that the dynamical transition behaviour of the protein solution resembles that of the pure solvent (Bizzarri et al 2000;Reat et al 2000;Daniel et al 2003).…”

Section: Solvent Role In the Protein-glass Transitionmentioning

confidence: 99%

Structure, dynamics and reactions of protein hydration water

Smith

Merzel

Bondar

et al. 2004

Phil. Trans. R. Soc. Lond. B

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The apparent simplicity of the water molecule belies the wide range of fascinating protein phenomena in which it participates. We review recent computer simulation work on buried, internal water molecules, discussing the thermodynamics of water molecule binding and the participation of water in proton transfer reactions. Surface water molecules are also considered, with emphasis on the modification of average solvent structure on a protein surface, the role of water in the protein dynamical 'glass' transition and a simplified description of the protein motions thereby activated.

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“…ions) are exchanged between water and amino acids in the proteins (Tsui et al 1999;Eyles and Kaltashov 2004;Pan et al 2010;Chen et al 2010;Gruebele 2010). However, a detailed understanding of folding is still missing due to the high dimensionality of the protein conformational spaces and by the wide range of relevant time scales (Daniel et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation exploration of unfolding and refolding of a ten-amino acid miniprotein

Zhao

Cheng

2011

Amino Acids

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Steered molecular dynamics simulations are performed to explore the unfolding and refolding processes of CLN025, a 10-residue beta-hairpin. In unfolding process, when CLN025 is pulled along the termini, the forceextension curve goes back and forth between negative and positive values not long after the beginning of simulation. That is so different from what happens in other peptides, where force is positive most of the time. The abnormal phenomenon indicates that electrostatic interaction between the charged termini plays an important role in the stability of the beta-hairpin. In the refolding process, the collapse to beta-hairpin-like conformations is very fast, within only 3.6 ns, which is driven by hydrophobic interactions at the termini, as the hydrophobic cluster involves aromatic rings of Tyr1, Tyr2, Trp9, and Tyr10. Our simulations improve the understanding on the structure and function of this type of miniprotein and will be helpful to further investigate the unfolding and refolding of more complex proteins.

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The Role of Dynamics in Enzyme Activity

Cited by 322 publications

References 140 publications

RETRACTED: Local Encoding of Computationally Designed Enzyme Activity

RETRACTED: Local Encoding of Computationally Designed Enzyme Activity

Structure, dynamics and reactions of protein hydration water

Molecular dynamics simulation exploration of unfolding and refolding of a ten-amino acid miniprotein

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