Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity
The nerve tissue hemoglobin of Cerebratulus lacteus (CerHb) is the smallest naturally occurring known hemoglobin. Stabilization of the diatomic bound, species (e.g., O2) is achieved through a network of hydrogen bonds based on three key residues TyrB10, GlnE7, and ThrE11. The first two residues are...
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todo:paper_08873585_v62_n3_p641_Marti2023-10-03T15:40:50Z Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity Martí, M.A. Bikiel, D.E. Crespo, A. Nardini, M. Bolognesi, M. Estrin, D.A. Computer simulation Density functional theory Hemoglobin Molecular dynamics Myoglobin Neural hemoglobin Quantum mechanical-molecular mechanical (QM-MM) carbon monoxide heme hemoglobin oxygen Aplysia article Cerebratulus lacteus computer simulation density functional theory dissociation constant energy transfer enzyme active site geometry hydrogen bond molecular dynamics nervous tissue nonhuman oxygen affinity priority journal quantum mechanics site directed mutagenesis Amino Acid Substitution Animals Annelida Binding Sites Heme Hemoglobins Humans Hydrogen Bonding Kinetics Models, Molecular Mutagenesis, Site-Directed Oxyhemoglobins Protein Structure, Secondary Recombinant Proteins Aplysia Cerebratulus lacteus The nerve tissue hemoglobin of Cerebratulus lacteus (CerHb) is the smallest naturally occurring known hemoglobin. Stabilization of the diatomic bound, species (e.g., O2) is achieved through a network of hydrogen bonds based on three key residues TyrB10, GlnE7, and ThrE11. The first two residues are typically associated in hemoglobins with enhanced O2 affinity, related to hydrogen bond stabilization of the heme-bound O2 resulting in a decrease of the ligand dissociation rates. In contrast to the above observations, the affinity of CerHb for O2 is only moderate, and the rate of O2 dissociation is unexpectedly high. To gain insight on the diverse molecular mechanisms controlling ligand affinities, we have analyzed w.t. CerHb and its ThrE11→Val mutant by means of joint molecular dynamics and quantum mechanics simulation techniques, complementing recent site-directed mutagenesis experiments. Our results suggest that the observed O2 dissociation rates can only be explained through a dynamic equilibrium between high and low affinity states of the w.t. CerHb heme distal site. © 2005 Wiley-Liss, Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08873585_v62_n3_p641_Marti |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Computer simulation Density functional theory Hemoglobin Molecular dynamics Myoglobin Neural hemoglobin Quantum mechanical-molecular mechanical (QM-MM) carbon monoxide heme hemoglobin oxygen Aplysia article Cerebratulus lacteus computer simulation density functional theory dissociation constant energy transfer enzyme active site geometry hydrogen bond molecular dynamics nervous tissue nonhuman oxygen affinity priority journal quantum mechanics site directed mutagenesis Amino Acid Substitution Animals Annelida Binding Sites Heme Hemoglobins Humans Hydrogen Bonding Kinetics Models, Molecular Mutagenesis, Site-Directed Oxyhemoglobins Protein Structure, Secondary Recombinant Proteins Aplysia Cerebratulus lacteus |
| spellingShingle |
Computer simulation Density functional theory Hemoglobin Molecular dynamics Myoglobin Neural hemoglobin Quantum mechanical-molecular mechanical (QM-MM) carbon monoxide heme hemoglobin oxygen Aplysia article Cerebratulus lacteus computer simulation density functional theory dissociation constant energy transfer enzyme active site geometry hydrogen bond molecular dynamics nervous tissue nonhuman oxygen affinity priority journal quantum mechanics site directed mutagenesis Amino Acid Substitution Animals Annelida Binding Sites Heme Hemoglobins Humans Hydrogen Bonding Kinetics Models, Molecular Mutagenesis, Site-Directed Oxyhemoglobins Protein Structure, Secondary Recombinant Proteins Aplysia Cerebratulus lacteus Martí, M.A. Bikiel, D.E. Crespo, A. Nardini, M. Bolognesi, M. Estrin, D.A. Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity |
| topic_facet |
Computer simulation Density functional theory Hemoglobin Molecular dynamics Myoglobin Neural hemoglobin Quantum mechanical-molecular mechanical (QM-MM) carbon monoxide heme hemoglobin oxygen Aplysia article Cerebratulus lacteus computer simulation density functional theory dissociation constant energy transfer enzyme active site geometry hydrogen bond molecular dynamics nervous tissue nonhuman oxygen affinity priority journal quantum mechanics site directed mutagenesis Amino Acid Substitution Animals Annelida Binding Sites Heme Hemoglobins Humans Hydrogen Bonding Kinetics Models, Molecular Mutagenesis, Site-Directed Oxyhemoglobins Protein Structure, Secondary Recombinant Proteins Aplysia Cerebratulus lacteus |
| description |
The nerve tissue hemoglobin of Cerebratulus lacteus (CerHb) is the smallest naturally occurring known hemoglobin. Stabilization of the diatomic bound, species (e.g., O2) is achieved through a network of hydrogen bonds based on three key residues TyrB10, GlnE7, and ThrE11. The first two residues are typically associated in hemoglobins with enhanced O2 affinity, related to hydrogen bond stabilization of the heme-bound O2 resulting in a decrease of the ligand dissociation rates. In contrast to the above observations, the affinity of CerHb for O2 is only moderate, and the rate of O2 dissociation is unexpectedly high. To gain insight on the diverse molecular mechanisms controlling ligand affinities, we have analyzed w.t. CerHb and its ThrE11→Val mutant by means of joint molecular dynamics and quantum mechanics simulation techniques, complementing recent site-directed mutagenesis experiments. Our results suggest that the observed O2 dissociation rates can only be explained through a dynamic equilibrium between high and low affinity states of the w.t. CerHb heme distal site. © 2005 Wiley-Liss, Inc. |
| format |
JOUR |
| author |
Martí, M.A. Bikiel, D.E. Crespo, A. Nardini, M. Bolognesi, M. Estrin, D.A. |
| author_facet |
Martí, M.A. Bikiel, D.E. Crespo, A. Nardini, M. Bolognesi, M. Estrin, D.A. |
| author_sort |
Martí, M.A. |
| title |
Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity |
| title_short |
Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity |
| title_full |
Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity |
| title_fullStr |
Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity |
| title_full_unstemmed |
Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin oxygen affinity |
| title_sort |
two distinct heme distal site states define cerebratulus lacteus mini-hemoglobin oxygen affinity |
| url |
http://hdl.handle.net/20.500.12110/paper_08873585_v62_n3_p641_Marti |
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