Genevieve Anne Holzapfel

Works (4)

Updated: July 5th, 2023 15:49

2020 article

Exploring the Rap1A Active Site Through Accelerated Molecular Dynamic Simulations

Schwabe, M., Holzapfel, G., & Mattos, C. (2020, April). FASEB JOURNAL, Vol. 34.

By: M. Schwabe *, G. Holzapfel n & C. Mattos*

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8. Decent Work and Economic Growth (OpenAlex)
Source: Web Of Science
Added: October 12, 2020

2015 journal article

Neutron Crystal Structure of RAS GTPase Puts in Question the Protonation State of the GTP gamma-Phosphate

JOURNAL OF BIOLOGICAL CHEMISTRY, 290(52), 31025–31036.

By: R. Knihtila*, G. Holzapfel n, K. Weiss *, F. Meilleur n  & C. Mattos n

MeSH headings : Catalysis; Guanosine Triphosphate / analogs & derivatives; Guanosine Triphosphate / chemistry; Guanosine Triphosphate / genetics; Guanosine Triphosphate / metabolism; Humans; Hydrolysis; Neutrons; Protein Structure, Tertiary; Proto-Oncogene Proteins p21(ras) / chemistry; Proto-Oncogene Proteins p21(ras) / genetics; Proto-Oncogene Proteins p21(ras) / metabolism
TL;DR: The neutron crystal structure of RAS bound to the GTP analogue GppNHp shows a protonated γ-phosphate at physiological pH, which counters the notion that the phosphate groups of GTP are fully deprotonated at the start of the hydrolysis reaction. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
8. Decent Work and Economic Growth (OpenAlex)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2012 journal article

Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

BIOCHEMISTRY, 51(31), 6114–6126.

By: G. Holzapfel n, G. Buhrman n & C. Mattos n

MeSH headings : Acetates / metabolism; Acetates / pharmacology; Allosteric Regulation / drug effects; Allosteric Site / drug effects; Calcium Compounds / metabolism; Calcium Compounds / pharmacology; Catalytic Domain; Dithioerythritol / metabolism; Dithioerythritol / pharmacology; Dithiothreitol / metabolism; Dithiothreitol / pharmacology; Enzyme Stability / drug effects; Guanosine Triphosphate / metabolism; Guanylyl Imidodiphosphate / chemistry; Hydrolysis; Isoenzymes / chemistry; Isoenzymes / metabolism; Models, Molecular; Polyethylene Glycols / pharmacology; Protein Structure, Secondary; Small Molecule Libraries / metabolism; Small Molecule Libraries / pharmacology; Solutions; Solvents / chemistry; Solvents / pharmacology; ras Proteins / chemistry; ras Proteins / metabolism
TL;DR: It is shown with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the "on" state, where the active site appears to be poised for catalysis (calcium acetate), or to what (via Semantic Scholar)
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8. Decent Work and Economic Growth (OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2010 journal article

Allosteric modulation of Ras positions Q61 for a direct role in catalysis

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(11), 4931–4936.

By: G. Buhrman n, G. Holzapfel n, S. Fetics n & C. Mattos n

author keywords: GTPase; Raf; calcium; intrinsic hydrolysis
MeSH headings : Acetates / pharmacology; Allosteric Regulation / drug effects; Allosteric Site; Biocatalysis / drug effects; Calcium / metabolism; Calcium Compounds / pharmacology; Catalytic Domain; Crystallography, X-Ray; Enzyme Stability / drug effects; Glutamine / metabolism; Hydrogen Bonding / drug effects; Hydrolysis / drug effects; Hydroxyl Radical / metabolism; Magnesium / metabolism; Models, Molecular; Protein Structure, Tertiary; Structure-Activity Relationship; ras Proteins / chemistry; ras Proteins / metabolism
TL;DR: This structure suggests a direct catalytic role for Q61 where it interacts with a water molecule that bridges one of the γ-phosphate oxygen atoms to the hydroxyl group of Y32 to stabilize the transition state of the hydrolysis reaction. (via Semantic Scholar)
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6. Clean Water and Sanitation (OpenAlex)
Source: Web Of Science
Added: August 6, 2018

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