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Open AccessJournal ArticleDOI

De novo design of helical bundles as models for understanding protein folding and function.

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TLDR
Structural and mutational analysis allowed us to explore the determinants of native protein structure and these determinants were then applied to the design of a dinuclear metal-binding protein that can now serve as a model for this important class of proteins.
Abstract
De novo protein design has proven to be a powerful tool for understanding protein folding, structure, and function. In this Account, we highlight aspects of our research on the design of dimeric, four-helix bundles. Dimeric, four-helix bundles are found throughout nature, and the history of their design in our laboratory illustrates our hierarchic approach to protein design. This approach has been successfully applied to create a completely native-like protein. Structural and mutational analysis allowed us to explore the determinants of native protein structure. These determinants were then applied to the design of a dinuclear metal-binding protein that can now serve as a model for this important class of proteins.

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Journal ArticleDOI

Supramolecular catalysis. Part 2: artificial enzyme mimics

TL;DR: Artificial catalysts and biomacromolecule hybrid catalysts which constitute good models towards the development of truly competitive artificial enzymes are presented.
Journal ArticleDOI

Design of folded peptides.

TL;DR: Examination of protein 3-dimensional structures suggests that complex tertiary folds and quaternary associations can be deconstructed into a limited number of secondary structural elements, such as strands, helices, and turns, which are assembled using loosely structured loops.
Journal ArticleDOI

Synthetic models for non-heme carboxylate-bridged diiron metalloproteins: strategies and tactics.

TL;DR: Two decades of progress in the development of small molecule synthetic model compounds for non-heme dinuclear iron-based metalloproteins is reviewed, including hemerythrin, which has been studied since the 1950s and has advanced the understanding of the mechanism.
Book ChapterDOI

The design of coiled-coil structures and assemblies

TL;DR: The current design rules for coiled coils are summarized, some of the key successful coiled-coil designs that have been created to date are described, and an important development in the field is shown; namely, new designs are being created with function as well as structure in mind.
References
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Journal ArticleDOI

Novel proteinaceous infectious particles cause scrapie

TL;DR: A new term "prion" is proposed to denote a small proteinaceous infectious particle which is resistant to inactivation by most procedures that modify nucleic acids.
Journal ArticleDOI

Dominant forces in protein folding

TL;DR: The present review aims to provide a reassessment of the factors important for folding in light of current knowledge, including contributions to the free energy of folding arising from electrostatics, hydrogen-bonding and van der Waals interactions, intrinsic propensities, and hydrophobic interactions.
Journal ArticleDOI

Protein misfolding, evolution and disease

TL;DR: This paper is a contribution from the Oxford Centre for Molecular Sciences, which is funded by the BBSRC, EPSRC and MRC.
Journal ArticleDOI

Sickle Cell Anemia, a Molecular Disease

TL;DR: The erythrocytes of certain individuals possess the capacity to undergo reversible changes in shape in response to changes in the partial pressure of oxygen, and these cells change their forms from the normal biconcave disk to crescent, holly wreath, and other forms.
Journal ArticleDOI

The CBP co-activator is a histone acetyltransferase

TL;DR: It is shown that CBP has intrinsic HAT activity, and Targeting CBP-associated H AT activity to specific promoters may be a mechanism by which E1A acts as a transcriptional activator.
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