Hydrophobic Effect Drives Oxygen Uptake in Myoglobin via Histidine E7

Boechi, Leonardo; Arrar, Mehrnoosh; Martí, Marcelo A.; Olson, John S.; Roitberg, Adrián E.; Estrin, Darı́o A.

doi:10.1074/jbc.m112.426056

Cited by 29 publications

(49 citation statements)

References 62 publications

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“…This finding, supported by others, [68,69] sparked a surge of applications that invoke the Jarzynski equality specifically using the ΔF J estimator. [3][4][5][6][7][8][9][10][11]70] Here, we have demonstrated, however, that if a work distribution is actually Gaussian, as was the case in Ref [46], ΔF FD is guaranteed to be more accurate than ΔF J .…”

Section: Discussionmentioning

confidence: 92%

“…Interest in the Jarzynski equality spread rapidly among the scientific community, not only among theoretical physicists but also among experimental biophysicists, who were eager to test and exploit its full potential, in particular in single-molecule pulling experiments. [3][4][5][6][7][8][9][10][11] In practice, the ensemble average indicated by the brackets hÁi in eq. 1 is estimated using the average of a finite sample of W 1 , …, W N values, resulting in the so-called Jarzynski free energy estimator ΔF J , where the hat notation indicates an estimator:…”

Section: Introductionmentioning

confidence: 99%

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On the accurate estimation of free energies using the jarzynski equality

et al. 2018

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The Jarzynski equality is one of the most widely celebrated and scrutinized nonequilibrium work theorems, relating free energy to the external work performed in nonequilibrium transitions. In practice, the required ensemble average of the Boltzmann weights of infinite nonequilibrium transitions is estimated as a finite sample average, resulting in the so‐called Jarzynski estimator, normalΔFfalse^J. Alternatively, the second‐order approximation of the Jarzynski equality, though seldom invoked, is exact for Gaussian distributions and gives rise to the Fluctuation‐Dissipation estimator normalΔFfalse^FD. Here we derive the parametric maximum‐likelihood estimator (MLE) of the free energy normalΔFfalse^ML considering unidirectional work distributions belonging to Gaussian or Gamma families, and compare this estimator to normalΔFfalse^J. We further consider bidirectional work distributions belonging to the same families, and compare the corresponding bidirectional normalΔFfalse^italicML∗ to the Bennett acceptance ratio (normalΔFfalse^BAR) estimator. We show that, for Gaussian unidirectional work distributions, normalΔFfalse^FD is in fact the parametric MLE of the free energy, and as such, the most efficient estimator for this statistical family. We observe that normalΔFfalse^ML and normalΔFfalse^italicML∗ perform better than normalΔFfalse^J and normalΔFfalse^BAR, for unidirectional and bidirectional distributions, respectively. These results illustrate that the characterization of the underlying work distribution permits an optimal use of the Jarzynski equality. © 2018 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

On the accurate estimation of free energies using the jarzynski equality

et al. 2018

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“…At present, the reason for such heterogeneity is unclear, though it might emerge from the presence of distinct conformations of the CD region, affecting the junction with E helix, the presence of different His tautomers [35] or even heme orientations [36]. Both configurations are characterized by rates that lead to a decrease in the hexacoordination equilibrium constant in comparison to that of Ngb.…”

Section: Discussionmentioning

confidence: 92%

Engineered chimeras reveal the structural basis of hexacoordination in globins: A case study of neuroglobin and myoglobin

Boron

Capece

Pennacchietti

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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While these results confirm the regulatory role of the CD region for bis-histidyl hexacoordination, they also suggest that additional sources contribute to fine tune the equilibrium. General significance Globins constitute a ubiquitous group of heme proteins widely found in all kingdoms of life. These findings raise challenging questions regarding the structure-function relationships in these proteins, as bis-histidyl hexacoordination emerges as a novel regulatory mechanism of the physiological function of globins.

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“…S1, B and D). Meanwhile, most of the side chains of the hydrophilic residues point away from the active site: Lys 22 , Arg 28 , His 46 , Lys 140 , Thr 144 , and Asp 145 (Fig. S1, B and C).…”

Section: A Mechanism For O 2 Enrichment In An Extradiol Dioxygenasementioning

confidence: 99%

“…The histidine gate hypothesis was proposed by Perutz and Mathews (21) to demonstrate the HisE7 in the distal region controls the ligand migration rate by a conformation change from an open to a closed status. Boechi et al (22) described that the hydrophobic effect around HisE7 is the major driving force for oxygen uptake other than steric hindrance from HisE7. Moreover, Cohen and Schulten (23) compared the characters of O 2 migration pathway in 12 monomeric globins from a broad range of species.…”

Section: Structural Requirement For Capturing O 2 In Iron-dependent Pmentioning

confidence: 99%

Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities

Yang

Liu

2018

Journal of Biological Chemistry

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3-Hydroxyanthranilate 3,4-dioxygenase (HAO) is an iron-dependent protein that activates O and inserts both oxygen atoms into 3-hydroxyanthranilate (3-HAA). An intriguing question is how HAO can rapidly bind O, even though local O concentrations and diffusion rates are relatively low. Here, a close inspection of the HAO structures revealed that substrate- and inhibitor-bound structures exhibit a closed conformation with three hydrophobic loop regions moving toward the catalytic iron center, whereas the ligand-free structure is open. We hypothesized that these loop movements enhance O binding to the binary complex of HAO and 3-HAA. We found that the carboxyl end of 3-HAA triggers changes in two loop regions and that the third loop movement appears to be driven by an H-bond interaction between Asn and Ile Mutational analyses revealed that N27A, I142A, and I142P variants cannot form a closed conformation, and steady-state kinetic assays indicated that these variants have a substantially higher for O than WT HAO. This observation suggested enhanced hydrophobicity at the iron center resulting from the concerted loop movements after the binding of the primary substrate, which is hydrophilic. Given that O is nonpolar, the increased hydrophobicity at the iron center of the binary complex appears to be essential for rapid O binding and activation, explaining the reason for the 3-HAA-induced loop movements. Because substrate binding-induced open-to-closed conformational changes are common, the results reported here may help further our understanding of how oxygen is enriched in nonheme iron-dependent dioxygenases.

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Hydrophobic Effect Drives Oxygen Uptake in Myoglobin via Histidine E7

Cited by 29 publications

References 62 publications

On the accurate estimation of free energies using the jarzynski equality

On the accurate estimation of free energies using the jarzynski equality

Engineered chimeras reveal the structural basis of hexacoordination in globins: A case study of neuroglobin and myoglobin

Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities

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