Disulfide bond influence on protein structural dynamics probed with 2D-IR vibrational echo spectroscopy

Ishikawa, Hiromasa; Kim, Seongheun; Kwak, Kyungwon; Wakasugi, Keisuke; Fayer, M. D.

doi:10.1073/pnas.0709760104

Cited by 64 publications

(88 citation statements)

References 48 publications

(97 reference statements)

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“…The results show the C35A structure to be more compact compared to the native structure. A similar trend is also observed in the case of human neuroglobin [35].…”

Section: Discussionsupporting

confidence: 64%

Influence of Disulfide Bonds on the Conformation of the Antifungal Protein from Oliver

Jayanthi¹,

Kangueane²,

Prakash³

et al. 2009

TOSBJ

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Abstract:The three-dimensional structure of a cysteine rich antifungal protein EAFP2 is found to be compact and extremely stable. The rigid nature of the protein is attributed to the presence of five disulfide bonds. However, the effect of individual disulfide bonds on the conformation has not been characterized. Thus, Molecular Dynamics (MD) simulations are used to explicate the influence of disulfide bonds on the conformation. In the present study, the cysteine residues in the native structure are mutated to alanine and the structural characteristics and conformational dynamics of the native and mutant structures are analyzed to better understand the effect of disulfide bonds on the tertiary structure. The simulated native and single mutant structures are found to posses similar conformations, indicating that loss of disulfide bond did not affect the tertiary structure conformation greatly. However, in the single mutant (C7A) structure, the N and C-terminal segments are found to be different. It is also interesting to note that the loss of disulfide bond between Cys35 and Cys39 actually resulted in a more compact structure.

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“…The results show the C35A structure to be more compact compared to the native structure. A similar trend is also observed in the case of human neuroglobin [35].…”

Section: Discussionsupporting

confidence: 64%

Influence of Disulfide Bonds on the Conformation of the Antifungal Protein from Oliver

Jayanthi¹,

Kangueane²,

Prakash³

et al. 2009

TOSBJ

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“…Two-dimensional IR spectroscopy probes the FFCF, and thereby the protein motions that are sensed by the transition-state analogue (the IR chromophore), only for a few tens of picoseconds at most. Although these experiments cannot identify the time scales for spectral diffusion for motions that occur beyond this time range, they do characterize the distribution of frequencies determined by the distribution of structures resulting from these slower motions (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)44). Motions at all time scales contribute to the initial value of the FFCF, but only those motions that occur on the femtosecond to picosecond time scale contribute to the FFCF decay probed in the 2D IR measurements.…”

Section: Discussionmentioning

confidence: 99%

“…A close experimental approximation to this ideal is to study the dynamics of an enzyme in a complex with a transition-state-analog inhibitor. There have been several infrared spectroscopic studies of enzyme-ligand interaction dynamics with substrate-analog complexes that mimic the ground state (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). These studies use infrared echo and 2D IR spectroscopies to measure the frequencyfrequency time correlation function (FFCF) that reveals the time .…”

mentioning

confidence: 99%

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Bandaria

Dutta

Nydegger

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

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The potential for femtosecond to picosecond time-scale motions to influence the rate of the intrinsic chemical step in enzymecatalyzed reactions is a source of significant controversy. Among the central challenges in resolving this controversy is the difficulty of experimentally characterizing thermally activated motions at this time scale in functionally relevant enzyme complexes. We report a series of measurements to address this problem using twodimensional infrared spectroscopy to characterize the time scales of active-site motions in complexes of formate dehydrogenase with the transition-state-analog inhibitor azide (N − 3 ). We observe that the frequency-frequency time correlation functions (FFCF) for the ternary complexes with NAD þ and NADH decay completely with slow time constants of 3.2 ps and 4.6 ps, respectively. This result suggests that in the vicinity of the transition state, the active-site enzyme structure samples a narrow and relatively rigid conformational distribution indicating that the transition-state structure is well organized for the reaction. In contrast, for the binary complex, we observe a significant static contribution to the FFCF similar to what is seen in other enzymes, indicating the presence of the slow motions that occur on time scales longer than our measurement window. 2D IR spectroscopy | enzyme dynamicsT he functional role of protein motions at the femtosecond to picosecond time scale is a hotly debated topic in enzymology. Although such a role could be general in nature, many experimental (1-10) and theoretical (11-23) studies of enzymecatalyzed hydrogen transfers have invoked protein motions at this time scale to explain anomalous kinetic isotope effects (KIE) and their temperature dependence. These studies result in the development of theoretical models, often referred to as Marcus-like models, in which the environmental reorganization that precedes the hydrogen-tunneling event has evolved to optimize the conformation of the transition state for tunneling (1,7,24). Fig. 1 illustrates the physical picture underlying such models. Heavy atom motions along the reorganization coordinate carry the system to a point where the donor and acceptor wells in the double-well hydrogen atom potential are degenerate and tunneling can proceed. At this position, the donor-acceptor distance and its fluctuations determine the tunneling probability. Mathematically, the rate constant for hydrogen transfer in these models is given by expressions of the form where C is the fraction of reactive complexes, the first exponential, in analogy with the Marcus theory for electron transfer, reflects the reorganization of the heavy atoms that modulates the relative energies of the reactants and the products to minimize the energy defect between the zero-point levels of the donor and acceptor wells. ΔG°is the driving force for the reaction, and λ is the reorganization energy. The second exponential gives the overlap between the donor and acceptor wave functions as a function of the donor-acceptor distan...

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“…The residues remain very close during the simulations, allowing easier formation of the disulfide bridge than in human Ngb. Disulfide formation in human Ngb has been experimentally shown to decrease protein flexibility (41), particularly, in the CD region. This in turn enhances O 2 affinity about 10-fold by stabilizing the 5c state, making the protein adopt a conformation prone to bind exogenous ligands (10,21).…”

Section: Discussionmentioning

confidence: 99%

Structure and dynamics of Antarctic fish neuroglobin assessed by computer simulations

Boron¹,

Russo²,

Boechi³

et al. 2011

IUBMB Life

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Neuroglobin (Ngb) is a heme protein, highly conserved along evolution, predominantly found in the nervous system. It is upregulated by hypoxia and ischemia and may have a neuroprotective role under hypoxic stress. Although many other roles have been proposed, the physiological function is still unclear. Antarctic icefishes lack hemoglobin and some species also lack myoglobin, but all have Ngb and thus may help the elucidation of Ngb function. We present the first theoretically derived structure of fish Ngb and describe its behavior using molecular dynamics simulations. Specifically, we sequenced and analyzed Ngbs from a colorless‐blooded Antarctic icefish species Chaenocephalus aceratus and a related red‐blooded species (Dissostichus mawsoni). Both fish Ngbs are 6‐coordinated but have some peculiarities that differentiate them from mammalian counterparts: they have extensions in the N and C termini that can interact with the EF loop, and a gap in the alignment that changes the CD‐region structure/dynamics that has been found to play a key role in human neuroglobin. Our results suggest that a single mutation between both fish Ngbs is responsible for significant difference in the behavior of the proteins. The functional role of these characteristics is discussed. © 2011 IUBMB IUBMB Life, 63(3): 206–213, 2011

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Disulfide bond influence on protein structural dynamics probed with 2D-IR vibrational echo spectroscopy

Cited by 64 publications

References 48 publications

Influence of Disulfide Bonds on the Conformation of the Antifungal Protein from Oliver

Influence of Disulfide Bonds on the Conformation of the Antifungal Protein from Oliver

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Structure and dynamics of Antarctic fish neuroglobin assessed by computer simulations

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