Nuclear magnetic resonance spectra and conformation of 1,4-dihydropyridines

Meyer, Walter L.; Mahler, Henry R.; Baker, Robert Horace

doi:10.1016/0006-3002(62)90744-8

Cited by 60 publications

(33 citation statements)

References 11 publications

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“…23,25,27 The molecular dynamics model obtained here is highly folded in comparison with typical enzyme-bound NAD + , but less compact than models based on chemical shift data, 23,[25][26][27] inferred from crystal packing, 19 or predicted from molecular mechanics calculations. 50 The fraction of time spent in a folded conformation estimated from the simulation is higher than that deduced from NMR data; [26][27][28][29] however, the definition of "folded" is open to interpretation, and the accuracy of these experimental values could be questioned considering the disagreement concerning the interpretation of the NMR data 34 and the influence of counter ions. 19 One important consideration is that the present simulations may not have sampled all the possible conformations of NAD + in solution, and this could explain some of the discrepancy in the calculated ratio of folded to unfolded forms.…”

Section: Discussionmentioning

confidence: 98%

Molecular Dynamics Simulations of NAD⁺ in Solution

Smith

Tanner

1999

J. Am. Chem. Soc.

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Molecular dynamics simulations in explicit solvent have been performed to investigate the conformational preferences of NAD + in solution. Two simulations, started from different initial conformations, generated similar results. Transitions between different folded forms of the molecule were observed. The simulations predict that the predominant form of NAD + in solution is a folded conformation characterized by a nicotinamide-adenine inter-ring distance of 0.52 nm, an angle of 148°between the aromatic ring planes, parallel glycosyl bond vectors, and the nicotinamide B side facing the adenine ring. Analysis of the NAD + conformations generated during the simulations suggests that folded conformations are favored over extended ones due to the reduction in solvent-accessible surface area, while differences between folded conformations correlate with changes in the solvation properties of the nicotinamide group. The simulation results are consistent with NMR relaxation data, and they argue against previous proposals that intimate, parallel ring stacking is the hallmark of the folded conformation of NAD + .

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Section: Discussionmentioning

confidence: 98%

Molecular Dynamics Simulations of NAD⁺ in Solution

Smith

Tanner

1999

J. Am. Chem. Soc.

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“…NAD is C, C 8 of adenine, D, C 2 of adenine, E, C 2 of nicotinamide, F, C 6 of nicotinamide, and G, C 4 of nicotinamide. Assignments based on Sarma et al (1968), Meyer et al (1962), and Jardetzky and Wade- Jardetzky (1966). conversion to NAD 1 .…”

Section: Nadh Photolysis Productsmentioning

confidence: 99%

NADH Enzyme-Dependent Fluorescence Recovery after Photobleaching (ED-FRAP): Applications to Enzyme and Mitochondrial Reaction Kinetics, In Vitro

Joubert

Fales

Wen

et al. 2004

Biophysical Journal

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NADH enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) was evaluated for studying enzyme kinetics in vitro and in isolated mitochondria. Mass, optical, and nuclear magnetic resonance spectroscopy data were consistent with the UV NADH photolysis reaction being NADH --> NAD* + H+ + e-. The overall net reaction was O2 + 2NADH + 2H+ --> 2NAD+ + 2H2O, or in the presence of other competing electron acceptors such as cytochrome c, NADH + 2Cyt(ox) --> NAD+ + H+ + 2Cyt(red). Solution pH could differentiate between these free-radical scavenging pathways. These net reactions represent the photooxidation of NADH to NAD+. Kinetic models and acquisition schemes were developed, varying [NADH] and [NAD] by altering NADH photolysis levels, for extracting kinetic parameters. UV irradiation levels used did not damage mitochondrial function or enzymatic activity. In mitochondria, [NADH] is a high affinity product inhibitor that significantly reduced the NADH regeneration rate. Matrix NADH regeneration only slightly exceeded the net rate of NADH consumption, suggesting that the NADH regeneration process is far from equilibrium. Evaluation of NADH regeneration in active mitochondria, in comparison to rotenone-treated preparations, revealed other regulatory elements in addition to matrix [NADH] and [NAD] that have yet to be fully characterized. These studies demonstrate that the rapid UV photolysis of NADH to NAD is an effective tool in evaluating the steady-state kinetic properties of enzyme systems. Initial data support the notion that the NADH regeneration process is far from equilibrium in mitochondria and is potentially controlled by NADH levels as well as several other matrix factors.

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“…Although the results of NMR experiments 20,21 and theoretical studies 22,23 unambiguously suggest the existence of numerous possible conformations in NADH, several authors since the work of Meyer et al 24 attributed all possible conformations into two main groups: folded, where the NA and AD rings are stacked, and unfolded (more extended) form where the rings are well-separated from each other. [15][16][17][18][19]25,26 An important role of the NADH conformations in the excited state dynamics was manifested by investigations of direct intramolecular energy transfer between the AD and NA moieties under excitation within the UV absorption band at 260 nm.…”

Section: Introductionmentioning

confidence: 99%

Two-Photon Excited Fluorescence Dynamics in NADH in Water–Methanol Solutions: The Role of Conformation States

et al. 2020

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The dynamics of polarized fluorescence in reduced nicotinamide adenine dinucleotide (NADH) at 460 nm under two-photon excitation at 720 nm by femtosecond laser pulses in water−methanol solutions has been studied experimentally and theoretically as a function of methanol concentration. A number of fluorescence parameters have been determined from experiment by means of the global fit procedure and then compared with the results reported by other authors. A comprehensive analysis of experimental errors was made. Ab initio calculations of the structure of NADH in water and methanol and of β-nicotinamide mononucleotide (NMNH) in vacuum have been carried out for clarifying the role of decay time heterogeneity. The main results obtained are as follows. An explanation of the heterogeneity in the measured fluorescence decay times in NADH has been suggested based on the influence of the internal molecular electric field in the nicotinamide ring on nonradiative decay rates. We suggest that different charge distributions in the cis and trans configurations result in different internal electrostatic field distributions that lead to the decay time heterogeneity. A slight but noticeable rise of the fluorescence decay times τ 1 and τ 2 with methanol concentration was observed and treated as a minor effect of a nonradiative relaxation slowing due to the decrease in solution polarity. Relative concentrations of the folded and unfolded NADH conformations in solutions have been determined using a new method of analysis of the rotational diffusion time τ r as a function of methanol concentration on the basis of the Stokes−Einstein−Debye equation. The analysis of the fluorescence anisotropy parameters obtained under linearly and circularly polarized excitation and the parameter Ω has been carried out and resulted in the determination of the two-photon excitation tensor components and suggested the existence of two excitation channels with comparable intensities. These were the longitudinal excitation channel dominated by the diagonal tensor component S zz and the mixed excitation channel dominated by the off-diagonal tensor components |S xz 2 + S yz 2 | 1/2 .

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Nuclear magnetic resonance spectra and conformation of 1,4-dihydropyridines

Cited by 60 publications

References 11 publications

Molecular Dynamics Simulations of NAD⁺ in Solution

Molecular Dynamics Simulations of NAD⁺ in Solution

NADH Enzyme-Dependent Fluorescence Recovery after Photobleaching (ED-FRAP): Applications to Enzyme and Mitochondrial Reaction Kinetics, In Vitro

Two-Photon Excited Fluorescence Dynamics in NADH in Water–Methanol Solutions: The Role of Conformation States

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Nuclear magnetic resonance spectra and conformation of 1,4-dihydropyridines

Cited by 60 publications

References 11 publications

Molecular Dynamics Simulations of NAD+ in Solution

Molecular Dynamics Simulations of NAD+ in Solution

NADH Enzyme-Dependent Fluorescence Recovery after Photobleaching (ED-FRAP): Applications to Enzyme and Mitochondrial Reaction Kinetics, In Vitro

Two-Photon Excited Fluorescence Dynamics in NADH in Water–Methanol Solutions: The Role of Conformation States

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Molecular Dynamics Simulations of NAD⁺ in Solution

Molecular Dynamics Simulations of NAD⁺ in Solution