R1ρ Relaxation outside of the Fast-Exchange Limit

Trott, Oleg; Palmer, Arthur G.

doi:10.1006/jmre.2001.2466

Cited by 195 publications

(309 citation statements)

References 8 publications

(13 reference statements)

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“…2b). The RD experiments measure spin-relaxation rates in the rotating frame ( R 1ρ ) during a relaxation period in which a radiofrequency field is applied with variable offset (Ω 2π −1 , in Hz) and power (ω 2π −1 , in Hz) to suppress the chemical exchange contribution ( R ex ) to the transverse spin relaxation rate ( R 2 ) arising due to chemical exchange between the energetically more stable ground state (GS) and ES 27,28 .…”

Section: Tilting the Tautomeric Equilibriummentioning

confidence: 99%

“…Techniques based on NMR relaxation dispersion (RD) 27–29 make it possible to characterize low-abundance short-lived conformational states, or ‘excited states’ (ESs), in biomolecules 30 . Using NMR RD, we recently provided evidence that wobble G•T/U mismatches exist in dynamic equilibrium with tautomeric (ES1) and anionic (ES2) WC-like mismatches within DNA and RNA duplexes 8,31 .…”

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confidence: 99%

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Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Kimsey

Szymanski

Zahurancik

et al. 2018

Nature

134

183

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Tautomeric and anionic Watson-Crick-like mismatches play important roles in replication and translation errors through mechanisms that are not fully understood. Using NMR relaxation dispersion, we resolved a sequence-dependent kinetic network connecting G•T/U wobbles with three distinct Watson-Crick mismatches consisting of two rapidly exchanging tautomeric species (Genol•T/U⇌G•Tenol/Uenol; population <0.4%) and one anionic species (G•T−/U−; population ≈0.001% at neutral pH). Inserting the sequence-dependent tautomerization/ionization step into a minimal kinetic mechanism for correct incorporation during replication following initial nucleotide binding leads to accurate predictions of dG•dT misincorporation probability across different polymerases, pH conditions, and for a chemically modified nucleotide, and provides mechanisms for sequence-dependent misincorporation. Our results indicate that the energetic penalty for tautomerization/ionization accounts for ≈10−2−10−3–fold discrimination against misincorporation, which proceeds primarily via tautomeric dGenol•dT and dG•dTenol with contributions from anionic dG•dT− dominating at pH ≥8.4 or for some mutagenic nucleotides.

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Section: Tilting the Tautomeric Equilibriummentioning

confidence: 99%

mentioning

confidence: 99%

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Kimsey

Szymanski

Zahurancik

et al. 2018

Nature

134

183

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“…In analogy to relaxation dispersion measurements, both the magnitude and the sign of the chemical shift difference Δω of the exchanging species can be obtained from R 1ρ experiments (Trott & Palmer, 2002).…”

Section: Properties/structures Of Minor Statesmentioning

confidence: 99%

Protein dynamics and function from solution state NMR spectroscopy

Kovermann

Rogne

Wolf‐Watz

2016

Quart. Rev. Biophys.

148

122

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Abstract. It is well-established that dynamics are central to protein function; their importance is implicitly acknowledged in the principles of the Monod, Wyman and Changeux model of binding cooperativity, which was originally proposed in 1965. Nowadays the concept of protein dynamics is formulated in terms of the energy landscape theory, which can be used to understand protein folding and conformational changes in proteins. Because protein dynamics are so important, a key to understanding protein function at the molecular level is to design experiments that allow their quantitative analysis. Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited for this purpose because major advances in theory, hardware, and experimental methods have made it possible to characterize protein dynamics at an unprecedented level of detail. Unique features of NMR include the ability to quantify dynamics (i) under equilibrium conditions without external perturbations, (ii) using many probes simultaneously, and (iii) over large time intervals. Here we review NMR techniques for quantifying protein dynamics on fast (ps-ns), slow (μs-ms), and very slow (s-min) time scales. These techniques are discussed with reference to some major discoveries in protein science that have been made possible by NMR spectroscopy.

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“…Several groups have investigated exchange mechanisms in a variety of cases using T 1r and Carr-PurcellMeiboom-Gill (CPMG) pulse sequences (201)(202)(203)(204)(205)(206) (214,215).…”

Section: Mechanism Of T 1r Relaxation In Cartilagementioning

confidence: 99%

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

et al. 2006

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In this article, both sodium magnetic resonance (MR) and T 1r relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T 1r , a brief description of (i) principles of measuring T 1r relaxation, (ii) pulse sequences for computing T 1r relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T 1r in biological tissues and (v) effects of exchange and dipolar interaction on T 1r dispersion are discussed. Correlation of T 1r relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokineinduced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T 1r data from osteoarthritic specimens, animal models, healthy human subjects and as well from osteoarthritic patients are provided. The current status of T 1r relaxation mapping of cartilage and future directions is also discussed. Copyright # 2006 John Wiley & Sons, Ltd. KEYWORDS: cartilage; arthritis; spin-lock; T1rho; sodium; MRI OSTEOARTHRITIS Osteoarthritis (OA) affects more than half of the population above the age of 65 (1,2) and has a significant negative impact on the quality of life of elderly individuals (3). The economic costs in the USA from OA have been estimated to be more than 1% of the gross domestic product (4). OA is now increasingly viewed as a metabolically active joint disorder of diverse etiologies. The biochemistry of the disease is characterized by the following changes in cartilage: reduced proteoglycan (PG) concentration, possible changes in the size of collagen fibril and aggregation of PG, increased water content and increased rate of synthesis and degradation of matrix macromolecules. The earliest changes in the cartilage due to OA result in a partial breakdown in the proteoglyc...

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R1ρ Relaxation outside of the Fast-Exchange Limit

Cited by 195 publications

References 8 publications

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Protein dynamics and function from solution state NMR spectroscopy

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

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R1ρ Relaxation outside of the Fast-Exchange Limit

Cited by 195 publications

References 8 publications

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Dynamic basis for dG•dT misincorporation via tautomerization and ionization

Protein dynamics and function from solution state NMR spectroscopy

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage

Contact Info

Product

Resources

About

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage