FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2950146976> ?p ?o ?g. }

• W2950146976 abstract "Author(s): Kreitman, Margaux | Advisor(s): Hubbell, Wayne L | Abstract: Proteins in pre-existing conformational equilibria sample different conformational states, some of which have important functional roles. Among intermediate conformational states, some proteins adopt a molten globule (MG) structure, which is compact and contains a relatively high content of native-like secondary structure, but has fewer tertiary contacts. The MG is a dynamic, flexible intermediate that adapts to a variety of conformations. Growing evidence that the MG is a hub in conformational equilibria between folded states emphasizes its putative functional importance. While the MG states of many α-helical proteins have been thoroughly studied, our understanding of β-sheet protein dynamics is incomplete. The plasticity of MG-like states of intestinal fatty acid binding protein (I-FABP), a β-barrel protein, and the T4 lysozyme (T4L) L99A mutant, a predominately α-helical protein, are thought to facilitate binding of a variety of ligands to their large cavities (230 and 150 �^3 for I-FABP and T4L L99A, respectively). X-ray crystal and nuclear magnetic resonance structures of I-FABP and T4L L99A do not identify an open conformation that permits ligand entry, suggesting that a rare MG may be facilitative.Site-directed spin labeling and EPR spectroscopy (SDSL EPR) is a sensitive tool for identifying backbone dynamics, conformational exchange, and ligand binding of proteins. In this dissertation, a panel of EPR experiments (continuous wave ((CW)) EPR, saturation recovery, and double electron-electron resonance) provides information on nanosecond-microsecond timescale motions, their amplitudes, and the thermodynamic equilibrium between these states to lay a basis for the structure and dynamics of the I-FABP and T4L L99A MGs. These results are supported by other forms of optical spectroscopy (intrinsic fluorescence and dynamic light scattering).As a means to populate rare intermediates, hydrostatic pressure is known to shift conformational equilibria to populate intermediate states through cavity hydration or structure-relaxation mechanisms. Internal hydration of proteins has structural parallels with the MG state. A comparison of the acid pH-stabilized MG of I-FABP and its high pressure states reveals structural similarity, in support of a model for protein conformational equilibria that involves a limited number of discrete conformational states rather than a continuum of intermediate conformations.The MG-like character of the high pressure state of the T4 lysozyme cavity mutant L99A is also investigated using pressure-resolved CW EPR. In contrast with wild-type T4L, the L99A mutant shows site-specific smooth sigmoidal transitions with pressure that indicate a two-state equilibrium between the native and intermediate states. The goal of this work is to determine how cavity hydration affects the protein structure allosterically.The main goal of this dissertation is to characterize the extent of structural heterogeneity of the MG from the SDSL EPR perspective, which encompasses fluctuation amplitudes, motional timescale, and the thermodynamic equilibrium state of the MG." @default.
• W2950146976 created "2019-06-27" @default.
• W2950146976 creator A5076220438 @default.
• W2950146976 date "2019-01-01" @default.
• W2950146976 modified "2023-09-27" @default.
• W2950146976 title "Exploring the conformational space of cavity-containing proteins with pH, high pressure, and site-directed spin labeling electron paramagnetic resonance" @default.
• W2950146976 hasPublicationYear "2019" @default.
• W2950146976 type Work @default.
• W2950146976 sameAs 2950146976 @default.
• W2950146976 citedByCount "0" @default.
• W2950146976 crossrefType "journal-article" @default.
• W2950146976 hasAuthorship W2950146976A5076220438 @default.
• W2950146976 hasConcept C116569031 @default.
• W2950146976 hasConcept C121332964 @default.
• W2950146976 hasConcept C12554922 @default.
• W2950146976 hasConcept C126838900 @default.
• W2950146976 hasConcept C1276947 @default.
• W2950146976 hasConcept C143409427 @default.
• W2950146976 hasConcept C170493617 @default.
• W2950146976 hasConcept C177462420 @default.
• W2950146976 hasConcept C185592680 @default.
• W2950146976 hasConcept C187961010 @default.
• W2950146976 hasConcept C193812863 @default.
• W2950146976 hasConcept C2775981520 @default.
• W2950146976 hasConcept C2777339483 @default.
• W2950146976 hasConcept C34742353 @default.
• W2950146976 hasConcept C46141821 @default.
• W2950146976 hasConcept C47701112 @default.
• W2950146976 hasConcept C55493867 @default.
• W2950146976 hasConcept C65154329 @default.
• W2950146976 hasConcept C71240020 @default.
• W2950146976 hasConcept C71924100 @default.
• W2950146976 hasConcept C8010536 @default.
• W2950146976 hasConcept C83042744 @default.
• W2950146976 hasConcept C86803240 @default.
• W2950146976 hasConceptScore W2950146976C116569031 @default.
• W2950146976 hasConceptScore W2950146976C121332964 @default.
• W2950146976 hasConceptScore W2950146976C12554922 @default.
• W2950146976 hasConceptScore W2950146976C126838900 @default.
• W2950146976 hasConceptScore W2950146976C1276947 @default.
• W2950146976 hasConceptScore W2950146976C143409427 @default.
• W2950146976 hasConceptScore W2950146976C170493617 @default.
• W2950146976 hasConceptScore W2950146976C177462420 @default.
• W2950146976 hasConceptScore W2950146976C185592680 @default.
• W2950146976 hasConceptScore W2950146976C187961010 @default.
• W2950146976 hasConceptScore W2950146976C193812863 @default.
• W2950146976 hasConceptScore W2950146976C2775981520 @default.
• W2950146976 hasConceptScore W2950146976C2777339483 @default.
• W2950146976 hasConceptScore W2950146976C34742353 @default.
• W2950146976 hasConceptScore W2950146976C46141821 @default.
• W2950146976 hasConceptScore W2950146976C47701112 @default.
• W2950146976 hasConceptScore W2950146976C55493867 @default.
• W2950146976 hasConceptScore W2950146976C65154329 @default.
• W2950146976 hasConceptScore W2950146976C71240020 @default.
• W2950146976 hasConceptScore W2950146976C71924100 @default.
• W2950146976 hasConceptScore W2950146976C8010536 @default.
• W2950146976 hasConceptScore W2950146976C83042744 @default.
• W2950146976 hasConceptScore W2950146976C86803240 @default.
• W2950146976 hasLocation W29501469761 @default.
• W2950146976 hasOpenAccess W2950146976 @default.
• W2950146976 hasPrimaryLocation W29501469761 @default.
• W2950146976 hasRelatedWork W1529006956 @default.
• W2950146976 hasRelatedWork W1974071773 @default.
• W2950146976 hasRelatedWork W2014132113 @default.
• W2950146976 hasRelatedWork W2065329227 @default.
• W2950146976 hasRelatedWork W2067183156 @default.
• W2950146976 hasRelatedWork W2098176418 @default.
• W2950146976 hasRelatedWork W2106063173 @default.
• W2950146976 hasRelatedWork W2108902702 @default.
• W2950146976 hasRelatedWork W2151683923 @default.
• W2950146976 hasRelatedWork W2163900048 @default.
• W2950146976 hasRelatedWork W2329253962 @default.
• W2950146976 hasRelatedWork W2471321162 @default.
• W2950146976 hasRelatedWork W2572480684 @default.
• W2950146976 hasRelatedWork W2585820310 @default.
• W2950146976 hasRelatedWork W2885793778 @default.
• W2950146976 hasRelatedWork W2912256178 @default.
• W2950146976 hasRelatedWork W3010005798 @default.
• W2950146976 hasRelatedWork W3087468879 @default.
• W2950146976 hasRelatedWork W3121358653 @default.
• W2950146976 hasRelatedWork W3194596948 @default.
• W2950146976 isParatext "false" @default.
• W2950146976 isRetracted "false" @default.
• W2950146976 magId "2950146976" @default.
• W2950146976 workType "article" @default.