Determination of ligand pathways in globins. Apolar tunnels versus polar gates
Although molecular dynamics simulations suggest multiple interior pathways for O 2 entry into and exit from globins, most experiments indicate well defined single pathways. In 2001, we highlighted the effects of large-to-small amino acid replacements on rates for ligand entry and exit onto the three...
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Language: | English |
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2012
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ftvliz:oai:oma.vliz.be:257443 2023-05-15T18:26:49+02:00 Determination of ligand pathways in globins. Apolar tunnels versus polar gates Salter, M. Blouin, G. Soman, J. Singleton, E. Dewilde, S. Moens, L. Pesce, A. Nardini, M. Bolognesi, M. Olson, J. 2012 application/pdf https://www.vliz.be/imisdocs/publications/346610.pdf en eng info:eu-repo/semantics/altIdentifier/wos/000309602100008 info:eu-repo/semantics/altIdentifier/doi/doi.org/10.1074/jbc.M112.392258 https://www.vliz.be/imisdocs/publications/346610.pdf info:eu-repo/semantics/openAccess %3Ci%3EJ.+Biol.+Chem.+287%2840%29%3C%2Fi%3E%3A+33163-33178.+%3Ca+href%3D%22https%3A%2F%2Fdx.doi.org%2F10.1074%2Fjbc.M112.392258%22+target%3D%22_blank%22%3Ehttps%3A%2F%2Fdx.doi.org%2F10.1074%2Fjbc.M112.392258%3C%2Fa%3E info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2012 ftvliz https://doi.org/10.1074/jbc.M112.392258 2022-05-01T10:40:19Z Although molecular dynamics simulations suggest multiple interior pathways for O 2 entry into and exit from globins, most experiments indicate well defined single pathways. In 2001, we highlighted the effects of large-to-small amino acid replacements on rates for ligand entry and exit onto the three-dimensional structure of sperm whale myoglobin. The resultant map argued strongly for ligand movement through a short channel from the heme iron to solvent that is gated by the distal histidine (His-64(E7)) near the solvent edge of the porphyrin ring. In this work, we have applied the same mutagenesis mapping strategy to the neuronal mini-hemoglobin from Cerebratulus lacteus (CerHb), which has a large internal tunnel from the heme iron to the C-terminal ends of the E and H helices, a direction that is 180° opposite to the E7 channel. Detailed comparisons of the new CerHb map with expanded results for Mb show unambiguously that the dominant (>90%) ligand pathway in CerHb is through the internal tunnel, and the major (>75%) ligand pathway in Mb is through the E7 gate. These results demonstrate that: 1) mutagenesis mapping can identify internal pathways when they exist; 2) molecular dynamics simulations need to be refined to address discrepancies with experimental observations; and 3) alternative pathways have evolved in globins to meet specific physiological demands. Article in Journal/Newspaper Sperm whale Flanders Marine Institute (VLIZ): Open Marine Archive (OMA) Journal of Biological Chemistry 287 40 33163 33178 |
institution |
Open Polar |
collection |
Flanders Marine Institute (VLIZ): Open Marine Archive (OMA) |
op_collection_id |
ftvliz |
language |
English |
description |
Although molecular dynamics simulations suggest multiple interior pathways for O 2 entry into and exit from globins, most experiments indicate well defined single pathways. In 2001, we highlighted the effects of large-to-small amino acid replacements on rates for ligand entry and exit onto the three-dimensional structure of sperm whale myoglobin. The resultant map argued strongly for ligand movement through a short channel from the heme iron to solvent that is gated by the distal histidine (His-64(E7)) near the solvent edge of the porphyrin ring. In this work, we have applied the same mutagenesis mapping strategy to the neuronal mini-hemoglobin from Cerebratulus lacteus (CerHb), which has a large internal tunnel from the heme iron to the C-terminal ends of the E and H helices, a direction that is 180° opposite to the E7 channel. Detailed comparisons of the new CerHb map with expanded results for Mb show unambiguously that the dominant (>90%) ligand pathway in CerHb is through the internal tunnel, and the major (>75%) ligand pathway in Mb is through the E7 gate. These results demonstrate that: 1) mutagenesis mapping can identify internal pathways when they exist; 2) molecular dynamics simulations need to be refined to address discrepancies with experimental observations; and 3) alternative pathways have evolved in globins to meet specific physiological demands. |
format |
Article in Journal/Newspaper |
author |
Salter, M. Blouin, G. Soman, J. Singleton, E. Dewilde, S. Moens, L. Pesce, A. Nardini, M. Bolognesi, M. Olson, J. |
spellingShingle |
Salter, M. Blouin, G. Soman, J. Singleton, E. Dewilde, S. Moens, L. Pesce, A. Nardini, M. Bolognesi, M. Olson, J. Determination of ligand pathways in globins. Apolar tunnels versus polar gates |
author_facet |
Salter, M. Blouin, G. Soman, J. Singleton, E. Dewilde, S. Moens, L. Pesce, A. Nardini, M. Bolognesi, M. Olson, J. |
author_sort |
Salter, M. |
title |
Determination of ligand pathways in globins. Apolar tunnels versus polar gates |
title_short |
Determination of ligand pathways in globins. Apolar tunnels versus polar gates |
title_full |
Determination of ligand pathways in globins. Apolar tunnels versus polar gates |
title_fullStr |
Determination of ligand pathways in globins. Apolar tunnels versus polar gates |
title_full_unstemmed |
Determination of ligand pathways in globins. Apolar tunnels versus polar gates |
title_sort |
determination of ligand pathways in globins. apolar tunnels versus polar gates |
publishDate |
2012 |
url |
https://www.vliz.be/imisdocs/publications/346610.pdf |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_source |
%3Ci%3EJ.+Biol.+Chem.+287%2840%29%3C%2Fi%3E%3A+33163-33178.+%3Ca+href%3D%22https%3A%2F%2Fdx.doi.org%2F10.1074%2Fjbc.M112.392258%22+target%3D%22_blank%22%3Ehttps%3A%2F%2Fdx.doi.org%2F10.1074%2Fjbc.M112.392258%3C%2Fa%3E |
op_relation |
info:eu-repo/semantics/altIdentifier/wos/000309602100008 info:eu-repo/semantics/altIdentifier/doi/doi.org/10.1074/jbc.M112.392258 https://www.vliz.be/imisdocs/publications/346610.pdf |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1074/jbc.M112.392258 |
container_title |
Journal of Biological Chemistry |
container_volume |
287 |
container_issue |
40 |
container_start_page |
33163 |
op_container_end_page |
33178 |
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1766208781239189504 |