Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d]
Like many hemoglobins, the structure of the dimeric hemoglobin from the clam Scapharca inaequivalvis is a “closed bottle” since there is no direct tunnel from the oxygen binding site on the heme to the solvent. The proximal histidine faces the dimer interface, which consists of the E and F helicies...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2015-03-01
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| Series: | F1000Research |
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| Online Access: | http://f1000research.com/articles/4-65/v1 |
| _version_ | 1818159244977897472 |
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| author | Kevin Trujillo Tasso Papagiannopoulos Kenneth W. Olsen |
| author_facet | Kevin Trujillo Tasso Papagiannopoulos Kenneth W. Olsen |
| author_sort | Kevin Trujillo |
| collection | DOAJ |
| description | Like many hemoglobins, the structure of the dimeric hemoglobin from the clam Scapharca inaequivalvis is a “closed bottle” since there is no direct tunnel from the oxygen binding site on the heme to the solvent. The proximal histidine faces the dimer interface, which consists of the E and F helicies. This is significantly different from tetrameric vertebrate hemoglobins and brings the heme groups near the subunit interface. The subunit interface is also characterized by an immobile, hydrogen-bonded network of water molecules. Although there is data which is consistent with the histidine gate pathway for ligand escape, these aspects of the structure would seem to make that pathway less likely. Locally enhanced sampling molecular dynamics are used here to suggest alternative pathways in the wild-type and six mutant proteins. In most cases the point mutations change the selection of exit routes observed in the simulations. Exit via the histidine gate is rarely seem although oxygen molecules do occasionally cross over the interface from one subunit to the other. The results suggest that changes in flexibility and, in some cases, creation of new cavities can explain the effects of the mutations on ligand exit paths. |
| first_indexed | 2024-12-11T15:42:55Z |
| format | Article |
| id | doaj.art-ef10ada859c34d2da6f893f6965bd357 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-11T15:42:55Z |
| publishDate | 2015-03-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-ef10ada859c34d2da6f893f6965bd3572022-12-22T00:59:46ZengF1000 Research LtdF1000Research2046-14022015-03-01410.12688/f1000research.6127.16565Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d]Kevin Trujillo0Tasso Papagiannopoulos1Kenneth W. Olsen2Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL, 60660, USADepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL, 60660, USADepartment of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL, 60660, USALike many hemoglobins, the structure of the dimeric hemoglobin from the clam Scapharca inaequivalvis is a “closed bottle” since there is no direct tunnel from the oxygen binding site on the heme to the solvent. The proximal histidine faces the dimer interface, which consists of the E and F helicies. This is significantly different from tetrameric vertebrate hemoglobins and brings the heme groups near the subunit interface. The subunit interface is also characterized by an immobile, hydrogen-bonded network of water molecules. Although there is data which is consistent with the histidine gate pathway for ligand escape, these aspects of the structure would seem to make that pathway less likely. Locally enhanced sampling molecular dynamics are used here to suggest alternative pathways in the wild-type and six mutant proteins. In most cases the point mutations change the selection of exit routes observed in the simulations. Exit via the histidine gate is rarely seem although oxygen molecules do occasionally cross over the interface from one subunit to the other. The results suggest that changes in flexibility and, in some cases, creation of new cavities can explain the effects of the mutations on ligand exit paths.http://f1000research.com/articles/4-65/v1Biomacromolecule-Ligand InteractionsProtein Chemistry & Proteomics |
| spellingShingle | Kevin Trujillo Tasso Papagiannopoulos Kenneth W. Olsen Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d] F1000Research Biomacromolecule-Ligand Interactions Protein Chemistry & Proteomics |
| title | Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d] |
| title_full | Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d] |
| title_fullStr | Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d] |
| title_full_unstemmed | Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d] |
| title_short | Effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of Scapharca inaequivalvis [v1; ref status: indexed, http://f1000r.es/52d] |
| title_sort | effects of mutations on the molecular dynamics of oxygen escape from the dimeric hemoglobin of scapharca inaequivalvis v1 ref status indexed http f1000r es 52d |
| topic | Biomacromolecule-Ligand Interactions Protein Chemistry & Proteomics |
| url | http://f1000research.com/articles/4-65/v1 |
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