Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility
The dynamics of Hemoglobin I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in molecular dynamics simulations. Features that account for difference...
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ftpubmed:oai:pubmedcentral.nih.gov:1544295 2023-05-15T18:26:45+02:00 Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility Fernandez-Alberti, S. Bacelo, D. E. Binning, R. C. Echave, J. Chergui, M. Lopez-Garriga, J. 2006-09-01 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1544295 http://www.ncbi.nlm.nih.gov/pubmed/16782787 https://doi.org/10.1529/biophysj.106.081646 en eng Biophysical Society http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1544295 http://www.ncbi.nlm.nih.gov/pubmed/16782787 http://dx.doi.org/10.1529/biophysj.106.081646 Copyright © 2006, Biophysical Society Biophysical Theory and Modeling Text 2006 ftpubmed https://doi.org/10.1529/biophysj.106.081646 2013-08-31T05:32:52Z The dynamics of Hemoglobin I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in molecular dynamics simulations. Features that account for differences in H2S affinity among the three have been examined. Our results verify the existence of an unusual heme rocking motion in unligated HbI that can promote the entrance of large ligands such as H2S. The FQF-mutant partially reproduces the amplitude and relative orientation of the motion of HbI's heme group. Therefore, besides introducing favorable electrostatic interactions with H2S, the three mutations in the distal pocket change the dynamic properties of the heme group. The active-site residues Gln-64(E7), Phe-43(CD1), and His-93(F8) are also shown to be more flexible in unligated HbI than in FQF-mutant and SW. Further contributions to H2S affinity come from differences in hydrogen bonding between the heme propionate groups and nearby amino acid residues. Text Sperm whale PubMed Central (PMC) Biophysical Journal 91 5 1698 1709 |
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English |
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Biophysical Theory and Modeling |
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Biophysical Theory and Modeling Fernandez-Alberti, S. Bacelo, D. E. Binning, R. C. Echave, J. Chergui, M. Lopez-Garriga, J. Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility |
topic_facet |
Biophysical Theory and Modeling |
description |
The dynamics of Hemoglobin I (HbI) from the clam Lucina pectinata, from wild-type sperm whale (SW) myoglobin, and from the L29F/H64Q/V68F triple mutant of SW, both unligated and bound to hydrogen sulfide (H2S), have been studied in molecular dynamics simulations. Features that account for differences in H2S affinity among the three have been examined. Our results verify the existence of an unusual heme rocking motion in unligated HbI that can promote the entrance of large ligands such as H2S. The FQF-mutant partially reproduces the amplitude and relative orientation of the motion of HbI's heme group. Therefore, besides introducing favorable electrostatic interactions with H2S, the three mutations in the distal pocket change the dynamic properties of the heme group. The active-site residues Gln-64(E7), Phe-43(CD1), and His-93(F8) are also shown to be more flexible in unligated HbI than in FQF-mutant and SW. Further contributions to H2S affinity come from differences in hydrogen bonding between the heme propionate groups and nearby amino acid residues. |
format |
Text |
author |
Fernandez-Alberti, S. Bacelo, D. E. Binning, R. C. Echave, J. Chergui, M. Lopez-Garriga, J. |
author_facet |
Fernandez-Alberti, S. Bacelo, D. E. Binning, R. C. Echave, J. Chergui, M. Lopez-Garriga, J. |
author_sort |
Fernandez-Alberti, S. |
title |
Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility |
title_short |
Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility |
title_full |
Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility |
title_fullStr |
Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility |
title_full_unstemmed |
Sulfide-Binding Hemoglobins: Effects of Mutations on Active-Site Flexibility |
title_sort |
sulfide-binding hemoglobins: effects of mutations on active-site flexibility |
publisher |
Biophysical Society |
publishDate |
2006 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1544295 http://www.ncbi.nlm.nih.gov/pubmed/16782787 https://doi.org/10.1529/biophysj.106.081646 |
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Sperm whale |
genre_facet |
Sperm whale |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1544295 http://www.ncbi.nlm.nih.gov/pubmed/16782787 http://dx.doi.org/10.1529/biophysj.106.081646 |
op_rights |
Copyright © 2006, Biophysical Society |
op_doi |
https://doi.org/10.1529/biophysj.106.081646 |
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Biophysical Journal |
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91 |
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5 |
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1698 |
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1709 |
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1766208728163418112 |