Sarah H. MacKenzie

Works (8)

Updated: July 5th, 2023 15:46

2016 journal article

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(41), E6080–E6088.

By: J. Maciag n, S. Mackenzie n, M. Tucker  n, J. Schipper n, P. Swartz n & A. Clark n

author keywords: allostery; conformational selection; saturation mutagenesis; protein solvation; protein structure
MeSH headings : Allosteric Regulation; Allosteric Site; Amino Acid Substitution; Caspase 3 / chemistry; Caspase 3 / genetics; Caspase 3 / metabolism; Catalytic Domain; Crystallography, X-Ray; Enzyme Activation; Models, Molecular; Molecular Conformation; Molecular Dynamics Simulation; Mutagenesis; Protein Binding; Protein Conformation; Protein Multimerization; Quantitative Structure-Activity Relationship; Solubility; Water / chemistry
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6. Clean Water and Sanitation (OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2014 journal article

Modifying Caspase-3 Activity by Altering Allosteric Networks

BIOCHEMISTRY, 53(48), 7582–7595.

By: C. Cade n, P. Swartz n, S. MacKenzie n & A. Clark n

MeSH headings : Allosteric Site / genetics; Amino Acid Substitution; Caspase 3 / chemistry; Caspase 3 / genetics; Caspase 3 / metabolism; Crystallography, X-Ray; Humans; Kinetics; Models, Molecular; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Conformation; Protein Multimerization; Protein Structure, Quaternary; Recombinant Proteins / chemistry; Recombinant Proteins / genetics; Recombinant Proteins / metabolism
TL;DR: The data show that the caspase-3 native ensemble includes the canonical active state as well as an inactive conformation characterized by an intact substrate-binding pocket, but with an altered helix 3, which reflects the relative population of each species in the native ensemble. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2014 journal article

Redesigning the procaspase-8 dimer interface for improved dimerization

Protein Science, 23(4), 442–453.

By: C. Ma, S. MacKenzie & A. Clark

Source: NC State University Libraries
Added: August 6, 2018

2013 journal article

Lengthening the Intersubunit Linker of Procaspase 3 Leads to Constitutive Activation

BIOCHEMISTRY, 52(36), 6219–6231.

By: S. MacKenzie n, J. Schipper n, E. England n, M. Thomas n, K. Blackburn n, P. Swartz n, A. Clark n

MeSH headings : Apoptosis / physiology; Caspase 3 / chemistry; Caspase 3 / genetics; Caspase 3 / metabolism; Caspase Inhibitors / pharmacology; Catalytic Domain; Enzyme Activation; Enzyme Precursors / chemistry; Models, Chemical; Models, Molecular; Molecular Dynamics Simulation; Protein Conformation; Protein Multimerization
TL;DR: The data show that releasing the strain of the short IL is not sufficient to populate the active conformer of the native ensemble, and it is shown that increasing the length of the IL by introducing 3-5 alanines results in constitutively active procaspases. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2013 journal article

Slow folding and assembly of a procaspase-3 interface variant

Biochemistry, 52(20), 3415–3427.

By: S. MacKenzie & A. Clark

Source: NC State University Libraries
Added: August 6, 2018

2011 journal article

A bifunctional allosteric site in the dimer interface of procaspase-3

BIOPHYSICAL CHEMISTRY, 159(1), 100–109.

By: J. Schipper n, S. MacKenzie n, A. Sharma n & A. Clark n

author keywords: Caspase; Apoptosis; Allosteric activator; Drug design; Cancer therapy
MeSH headings : Allosteric Site; Caspase 3 / chemistry; Caspase 3 / metabolism; Enzyme Activation / drug effects; Humans; Models, Molecular; Protein Binding; Protein Multimerization; Small Molecule Libraries / chemistry; Small Molecule Libraries / pharmacology
TL;DR: This work has utilized the allosteric site of caspase-3 to identify a small molecule activator of procaspase and to characterize its binding to the protease, and suggests that an efficient activator must stabilize the active conformer of the zymogen by expelling the intersubunit linker from the interface. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: Web Of Science, NC State University Libraries
Added: August 6, 2018

2010 review

The potential for caspases in drug discovery

[Review of ]. Current Opinion in Drug Discovery & Development, 13(5), 568–576.

By: S. MacKenzie, J. Schipper & A. Clark

Source: NC State University Libraries
Added: August 6, 2018

2008 review

Targeting cell death in tumors by activating Caspases

[Review of ]. Current Cancer Drug Targets, 8(2), 98–109.

By: S. MacKenzie & A. Clark

Source: NC State University Libraries
Added: August 6, 2018

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