Myoglobin-CO Conformational Substate Dynamics: 2D Vibrational Echoes and MD Simulations

Merchant, Kusai A.; Thompson, David E.; Xu, Qing‐Hua; Williams, Ryan B.; Loring, Roger F.; Fayer, M. D.

doi:10.1016/s0006-3495(02)75669-5

Cited by 51 publications

(133 citation statements)

References 42 publications

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“…5,8,10 The simulated dynamics overestimate the dynamical line broadening while underestimating the static line broadening needed to describe the experimental linear spectrum and vibrational echo data. However, analysis of the vibrational δω(t) ) δω p (t) + δω H64 (t) + δω s (t)…”

Section: Discussionmentioning

confidence: 93%

“…5,8,10,11,52 In this picture, the force exerted by the local electric field on the electric dipole of the CO induces a shift in the CO transition frequency. Therefore, the frequency fluctuates in time with the dynamics of the local electric field.…”

Section: Experimental and Computational Methodsmentioning

confidence: 99%

“…The combination of complementary spectroscopic and computational studies can provide a detailed and self-consistent picture of protein structure, dynamics, and function. 3,5,[8][9][10][11] The spectrally resolved infrared stimulated vibrational echo has been successfully applied to investigate protein structure and dynamics. 6,7,9,12,13 Application of this technique to heme proteins has focused on the CO bound to the active site.…”

Section: Introductionmentioning

confidence: 99%

“…Comparison of measured and simulated absorption spectra and vibrational echoes showed that the primary structural difference between A 1 and A 3 states could be assigned to a rotation of the singly protonated imidazole group of the distal histidine, H64. 5,8,10,11 A wealth of experimental and theoretical evidence underscores the importance of H64 in myoglobin function and dynamics. 23,[30][31][32][33] H64 is the most polar residue near the active site, and interacts strongly with both CO and O 2 ligands.…”

Section: Introductionmentioning

confidence: 99%

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Ultrafast Dynamics of Myoglobin without the Distal Histidine: Stimulated Vibrational Echo Experiments and Molecular Dynamics Simulations

et al. 2005

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Ultrafast protein dynamics of the CO adduct of a myoglobin mutant with the polar distal histidine replaced by a nonpolar valine (H64V) have been investigated by spectrally resolved infrared stimulated vibrational echo experiments and molecular dynamics (MD) simulations. In aqueous solution at room temperature, the vibrational dephasing rate of CO in the mutant is reduced by ∼50% relative to the native protein. This finding confirms that the dephasing of the CO vibration in the native protein is sensitive to the interaction between the ligand and the distal histidine. The stimulated vibrational echo observable is calculated from MD simulations of H64V within a model in which vibrational dephasing is driven by electrostatic forces. In agreement with experiment, calculated vibrational echoes show slower dephasing for the mutant than for the native protein. However, vibrational echoes calculated for H64V do not show the quantitative agreement with measurements demonstrated previously for the native protein.

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Section: Discussionmentioning

confidence: 93%

Section: Experimental and Computational Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ultrafast Dynamics of Myoglobin without the Distal Histidine: Stimulated Vibrational Echo Experiments and Molecular Dynamics Simulations

et al. 2005

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“…[6][7][8] It has been suggested that different electrostatic environments in the heme pocket arising from distinct structures are largely responsible for the observed bands. 9 The distal histidine His64 plays a prominent role in determining the CO stretching frequencies, but the tautomerization and orientation of this residue remain controversial.…”

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confidence: 99%

Structural Assignments and Dynamics of the A Substates of MbCO: Spectrally Resolved Vibrational Echo Experiments and Molecular Dynamics Simulations

et al. 2002

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Spectrally resolved three-pulse stimulated vibrational echo experiments are used as the basis for structural assignments of the A 1 and A 3 spectroscopic substates in the IR spectrum of the carbon monoxide (CO) stretch of carbonmonoxymyoglobin (MbCO). The measured dephasing dynamics of these substates is compared to the dephasing dynamics of MbCO predicted from molecular dynamics (MD) simulations. We assign the A 1 and A 3 substates to different protein conformations on the basis of the agreement between the measured and computed vibrational echoes. In the A 1 substate, the N -H proton and N δ of His64 are equidistant from the ligand, whereas in the A 3 substate, the N -H of His64 is oriented toward the CO.Structural information is essential for understanding the functions of proteins. Techniques such as X-ray diffraction, 1-3 neutron diffraction, 4 and 2D-NMR 5 have been used to investigate the structures of many proteins and a wide variety of other biomolecules. Despite the power of these methods, the identification of conformational substates that interconvert rapidly is difficult because of the limited time resolution of these techniques. A long-standing problem of this type is the assignment of the A conformational substates of the protein carbonmonoxymyoglobin (MbCO).The infrared (IR) spectrum of the CO stretching mode of MbCO has three absorption bands, denoted A 0 (∼1965 cm -1 ), A 1 (∼1944 cm -1 ), and A 3 (∼1930 cm -1 ), as shown in Figure 1. 6-8 It has been suggested that different electrostatic environments in the heme pocket arising from distinct structures are largely responsible for the observed bands. 9 The distal histidine His64 plays a prominent role in determining the CO stretching frequencies, but the tautomerization and orientation of this residue remain controversial. [1][2][3]10,11 His64 has two titratable nitrogens, N δ and N , either of which can be oriented toward the ligand through rotation of the imidazole ring. This residue is also fairly mobile and has been observed at a wide variety of distances from the CO ligand. 2,3,12 At low pH, His64 is thought to be doubly protonated and has been observed in the low pH crystal structure rotated out of the heme binding pocket away from the CO ligand. 12 This conformer, with little interaction between His64 and the ligand, is thought to correspond to the A 0 substate, because at low pH the A 0 line is the most intense IR absorption band. In addition, mutations of His64 to apolar residues produce an A substate band at approximately the same frequency as the A 0 line. 9,13 At pH greater than 6, the A 1 and A 3 substates are the most populated. 7,14 Crystal structures at neutral pH indicate that His64 is rotated into the heme pocket and is much closer to the ligand than in the A 0 substate, but the exact orientation of His64 is uncertain. 2,3 Also, the tautomerization state of the singly protonated His64 at neutral pH is unclear.Structural calculations have provided insight into the origins of the A 1 and A 3 substates. Rovira et al. 10 performed...

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Ultrafast Structural Fluctuations of Myoglobin‐Bound Thiocyanate and Selenocyanate Ions Measured with Two‐Dimensional Infrared Photon Echo Spectroscopy

2015

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Structural dynamics within the distal cavity of myoglobin protein is investigated using 2D-IR and IR pump-probe spectroscopy of the N≡C stretch modes of heme-bound thiocyanate and selenocyanate ions. Although myoglobin-bound thiocyanate group shows a doublet in its IR absorption spectrum, no cross peaks originating from chemical exchange between the two components are observed in the time-resolved 2D IR spectra within the experimental time window. Frequency-frequency correlation functions of the two studied anionic ligands are obtained by means of a few different analysis approaches; these functions were then used to elucidate the differences in structural fluctuation around ligand, ligand-protein interactions, and the degree of structural heterogeneity within the hydrophobic pocket of these myoglobin complexes.

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Myoglobin-CO Conformational Substate Dynamics: 2D Vibrational Echoes and MD Simulations

Cited by 51 publications

References 42 publications

Ultrafast Dynamics of Myoglobin without the Distal Histidine: Stimulated Vibrational Echo Experiments and Molecular Dynamics Simulations

Ultrafast Dynamics of Myoglobin without the Distal Histidine: Stimulated Vibrational Echo Experiments and Molecular Dynamics Simulations

Structural Assignments and Dynamics of the A Substates of MbCO: Spectrally Resolved Vibrational Echo Experiments and Molecular Dynamics Simulations

Ultrafast Structural Fluctuations of Myoglobin‐Bound Thiocyanate and Selenocyanate Ions Measured with Two‐Dimensional Infrared Photon Echo Spectroscopy

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