Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands†
The pKas of ferric aquo–heme and aquo–heme electrochemical midpoints (Ems) at pH 7 in sperm whale myoglobin, Aplysia myoblogin, hemoglobin I, heme oxygenase 1, horseradish peroxidase and cytochrome c oxidase were calculated with Multi-Conformation Continuum Electrostatics (MCCE). The pKas span 3.3 p...
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ftpubmed:oai:pubmedcentral.nih.gov:2727071 2023-05-15T18:26:50+02:00 Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† Song, Yifan Mao, Junjun Gunner, M. R. 2006-07-04 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727071 http://www.ncbi.nlm.nih.gov/pubmed/16800621 https://doi.org/10.1021/bi052182l en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727071 http://www.ncbi.nlm.nih.gov/pubmed/16800621 http://dx.doi.org/10.1021/bi052182l Article Text 2006 ftpubmed https://doi.org/10.1021/bi052182l 2013-09-02T15:45:22Z The pKas of ferric aquo–heme and aquo–heme electrochemical midpoints (Ems) at pH 7 in sperm whale myoglobin, Aplysia myoblogin, hemoglobin I, heme oxygenase 1, horseradish peroxidase and cytochrome c oxidase were calculated with Multi-Conformation Continuum Electrostatics (MCCE). The pKas span 3.3 pH units from 7.6 in heme oxygenase 1 to 10.9 in peroxidase, and the Ems range from −250 mv in peroxidase to 125 mV in Aplysia myoglobin. Proteins with higher in situ ferric aquo–heme pKas tend to have lower Ems. Both changes arise from the protein stabilizing a positively charged heme. However, compared with values in solution, the protein shifts the aquo–heme Ems more than the pKas. Thus, the protein has a larger effective dielectric constant for the protonation reaction, showing that electron and proton transfers are coupled to different conformational changes that are captured in the MCCE analysis. The calculations reveal a breakdown in the classical continuum electrostatic analysis of pairwise interactions. Comparisons with DFT calculations show that Coulomb’s law overestimates the large unfavorable interactions between the ferric water–heme and positively charged groups facing the heme plane by as much as 60%. If interactions with CuB in cytochrome c oxidase and Arg 38 in horseradish peroxidase are not corrected, the pKa calculations are in error by as much as 6 pH units. With DFT corrected interactions calculated pKas and Ems differ from measured values by less than 1 pH unit or 35 mV, respectively. The in situ aquo–heme pKa is important for the function of cytochrome c oxidase since it helps to control the stoichiometry of proton uptake coupled to electron transfer Text Sperm whale PubMed Central (PMC) Biochemistry 45 26 7949 7958 |
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Article Song, Yifan Mao, Junjun Gunner, M. R. Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† |
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description |
The pKas of ferric aquo–heme and aquo–heme electrochemical midpoints (Ems) at pH 7 in sperm whale myoglobin, Aplysia myoblogin, hemoglobin I, heme oxygenase 1, horseradish peroxidase and cytochrome c oxidase were calculated with Multi-Conformation Continuum Electrostatics (MCCE). The pKas span 3.3 pH units from 7.6 in heme oxygenase 1 to 10.9 in peroxidase, and the Ems range from −250 mv in peroxidase to 125 mV in Aplysia myoglobin. Proteins with higher in situ ferric aquo–heme pKas tend to have lower Ems. Both changes arise from the protein stabilizing a positively charged heme. However, compared with values in solution, the protein shifts the aquo–heme Ems more than the pKas. Thus, the protein has a larger effective dielectric constant for the protonation reaction, showing that electron and proton transfers are coupled to different conformational changes that are captured in the MCCE analysis. The calculations reveal a breakdown in the classical continuum electrostatic analysis of pairwise interactions. Comparisons with DFT calculations show that Coulomb’s law overestimates the large unfavorable interactions between the ferric water–heme and positively charged groups facing the heme plane by as much as 60%. If interactions with CuB in cytochrome c oxidase and Arg 38 in horseradish peroxidase are not corrected, the pKa calculations are in error by as much as 6 pH units. With DFT corrected interactions calculated pKas and Ems differ from measured values by less than 1 pH unit or 35 mV, respectively. The in situ aquo–heme pKa is important for the function of cytochrome c oxidase since it helps to control the stoichiometry of proton uptake coupled to electron transfer |
format |
Text |
author |
Song, Yifan Mao, Junjun Gunner, M. R. |
author_facet |
Song, Yifan Mao, Junjun Gunner, M. R. |
author_sort |
Song, Yifan |
title |
Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† |
title_short |
Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† |
title_full |
Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† |
title_fullStr |
Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† |
title_full_unstemmed |
Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands† |
title_sort |
electrostatic environment of hemes in proteins: pkas of hydroxyl ligands† |
publishDate |
2006 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727071 http://www.ncbi.nlm.nih.gov/pubmed/16800621 https://doi.org/10.1021/bi052182l |
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Sperm whale |
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Sperm whale |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727071 http://www.ncbi.nlm.nih.gov/pubmed/16800621 http://dx.doi.org/10.1021/bi052182l |
op_doi |
https://doi.org/10.1021/bi052182l |
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Biochemistry |
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45 |
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26 |
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7949 |
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7958 |
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1766208811190714368 |