Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant†
ABSTRACT: In the sperm whale myoglobin mutant H93G, the proximal histidine is replaced by glycine, leaving a cavity in which exogenous imidazole can bind and ligate the heme iron (Barrick, D. (1994) Biochemistry 33, 6545-6554). Structural studies of this mutant suggest that serine 92 may play an imp...
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ftciteseerx:oai:CiteSeerX.psu:10.1.1.574.3946 2023-05-15T18:26:48+02:00 Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† The Pennsylvania State University CiteSeerX Archives 1999 application/pdf http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.574.3946 http://www.stanford.edu/group/boxer/papers/paper173.pdf en eng http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.574.3946 http://www.stanford.edu/group/boxer/papers/paper173.pdf Metadata may be used without restrictions as long as the oai identifier remains attached to it. http://www.stanford.edu/group/boxer/papers/paper173.pdf text 1999 ftciteseerx 2016-01-08T12:40:53Z ABSTRACT: In the sperm whale myoglobin mutant H93G, the proximal histidine is replaced by glycine, leaving a cavity in which exogenous imidazole can bind and ligate the heme iron (Barrick, D. (1994) Biochemistry 33, 6545-6554). Structural studies of this mutant suggest that serine 92 may play an important role in imidazole binding by serving as a hydrogen bond acceptor. Serine 92 is highly conserved in myoglobins, forming a well-characterized weak hydrogen bond with the proximal histidine in the native protein. We have probed the importance of this hydrogen bond through studies of the double mutants S92A/H93G and S92T/H93G incorporating exogenous imidazole and methylimidazoles. 1H NMR spectra reveal that loss of the hydrogen bond in S92A/H93G does not affect the conformation of the bound imidazole. However, the binding constants for imidazoles to the ferrous nitrosyl complex of S92A/H93G are much weaker than in H93G. These results are discussed in terms of hydrogen bonding and steric packing within the proximal cavity. The results also highlight the importance of the trans diatomic ligand in altering the binding and sensitivity to perturbation of the ligand in the proximal cavity. Exogenous molecules which serve a specific structural or functional role can be inserted into engineered protein cavities as an extension of site-directed mutagenesis for Text Sperm whale Unknown |
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English |
description |
ABSTRACT: In the sperm whale myoglobin mutant H93G, the proximal histidine is replaced by glycine, leaving a cavity in which exogenous imidazole can bind and ligate the heme iron (Barrick, D. (1994) Biochemistry 33, 6545-6554). Structural studies of this mutant suggest that serine 92 may play an important role in imidazole binding by serving as a hydrogen bond acceptor. Serine 92 is highly conserved in myoglobins, forming a well-characterized weak hydrogen bond with the proximal histidine in the native protein. We have probed the importance of this hydrogen bond through studies of the double mutants S92A/H93G and S92T/H93G incorporating exogenous imidazole and methylimidazoles. 1H NMR spectra reveal that loss of the hydrogen bond in S92A/H93G does not affect the conformation of the bound imidazole. However, the binding constants for imidazoles to the ferrous nitrosyl complex of S92A/H93G are much weaker than in H93G. These results are discussed in terms of hydrogen bonding and steric packing within the proximal cavity. The results also highlight the importance of the trans diatomic ligand in altering the binding and sensitivity to perturbation of the ligand in the proximal cavity. Exogenous molecules which serve a specific structural or functional role can be inserted into engineered protein cavities as an extension of site-directed mutagenesis for |
author2 |
The Pennsylvania State University CiteSeerX Archives |
format |
Text |
title |
Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† |
spellingShingle |
Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† |
title_short |
Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† |
title_full |
Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† |
title_fullStr |
Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† |
title_full_unstemmed |
Hydrogen Bonding Modulates Binding of Exogenous Ligands in a Myoglobin Proximal Cavity Mutant† |
title_sort |
hydrogen bonding modulates binding of exogenous ligands in a myoglobin proximal cavity mutant† |
publishDate |
1999 |
url |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.574.3946 http://www.stanford.edu/group/boxer/papers/paper173.pdf |
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Sperm whale |
genre_facet |
Sperm whale |
op_source |
http://www.stanford.edu/group/boxer/papers/paper173.pdf |
op_relation |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.574.3946 http://www.stanford.edu/group/boxer/papers/paper173.pdf |
op_rights |
Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
_version_ |
1766208762642694144 |