Journal ArticleDOI
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.
David E. Coleman,Albert M. Berghuis,Ethan Lee,Maurine E. Linder,Alfred G. Gilman,Stephen R. Sprang +5 more
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TLDR
AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP.Abstract:
Mechanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein alpha subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. High-resolution x-ray structures of the GTP gamma S and GDP.AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues. Glutamine204 (Gln61 in p21ras) stabilizes and orients the hydrolytic water in the trigonal-bipyramidal transition state. Arginine 178 stabilizes the negative charge at the equatorial oxygen atoms of the pentacoordinate phosphate intermediate. Conserved only in the G alpha family, this residue may account for the higher hydrolytic rate of G alpha proteins relative to those of the p21ras family members. The fold of Gi alpha 1 differs from that of the homologous Gt alpha subunit in the conformation of a helix-loop sequence located in the alpha-helical domain that is characteristic of these proteins; this site may participate in effector binding. The amino-terminal 33 residues are disordered in GTP gamma S-Gi alpha 1, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP.read more
Citations
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Journal ArticleDOI
Catalytic site mutations confer multiple states of G protein activation
Natalie L. Hewitt,Ning Ma,Nadia Arang,Sarah A. Martin,Ajit Prakash,Jeffrey F. DiBerto,Kevin Knight,Soumadwip Ghosh,Reid H.J. Olsen,Bryan L. Roth,J. Silvio Gutkind,Nagarajan Vaidehi,Sharon L. Campbell,Henrik G. Dohlman +13 more
TL;DR: Hewitt et al. as discussed by the authors analyzed all possible substitutions of this residue in multiple Gα isoforms and found that some mutants were further activated and inactivated by G protein-coupled receptors.
DissertationDOI
Endogenous and exogenous modulation of regulator of G-protein signaling 4
TL;DR: To my loving parents, Carmen and Carlos, and my sister, Candice, for always believing in me ii ACKNOWLEDGMENTS
Journal ArticleDOI
Probing G-protein function.
TL;DR: Synthetic peptides are providing important insights into the nature and specificity of the G-protein α/effector interactions.
Journal ArticleDOI
Folding of Gα Subunits: Implications for Disease States.
Matthew S. Najor,Brian D. Leverson,Jesse Goossens,Saad Kothawala,Kenneth W. Olsen,Duarte Mota de Freitas +5 more
TL;DR: It was found that as the temperature increased, Gα subunits, which are known to be rich in α-helices, converted to proteins with increased content of β-sheets and random coil, and a π-cation interaction between essential arginine and tryptophan residues was shown to be a contributor to the stability of G α subunits.
Book ChapterDOI
Analysis of Water Molecules in the Hras-GTP and GDP Complexes with Molecular Dynamics Simulations
Takeshi Miyakawa,Ryota Morikawa,Masako Takasu,Akira Dobashi,Kimikazu Sugimori,Kazutomo Kawaguchi,Hiroaki Saito,Hidemi Nagao +7 more
TL;DR: In this article, the authors used AMBER03 and calculated force field parameters, and performed MD simulations of Hras-GTP and GDP complexes with water solvents, and found that the number of water molecules in the first hydration sphere is larger in GDP than in GTP.
References
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Journal ArticleDOI
PROCHECK: a program to check the stereochemical quality of protein structures
TL;DR: The PROCHECK suite of programs as mentioned in this paper provides a detailed check on the stereochemistry of a protein structure and provides an assessment of the overall quality of the structure as compared with well refined structures of the same resolution.
Journal ArticleDOI
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
G proteins: transducers of receptor-generated signals
TL;DR: This paper presents a meta-analysis of G Protein Interactions and its Foundations, which states that G Proteins are Law-Regulated and G Protein-Effector Interactions are Nonvolatile.
Journal ArticleDOI
Free R value: a novel statistical quantity for assessing the accuracy of crystal structures.
TL;DR: In this article, a statistical quantity (RfreeT) is defined to measure the agreement between observed and computed structure factor amplitudes for a 'test' set of reflections that is omitted in the modelling and refinement process.
Journal ArticleDOI
The GTPase superfamily: conserved structure and molecular mechanism
TL;DR: GTPases are conserved molecular switches, built according to a common structural design, and rapidly accruing knowledge of individual GTPases—crystal structures, biochemical properties, or results of molecular genetic experiments—support and generate hypotheses relating structure to function in other members of the diverse family of GTPase.