Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition
Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO), numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and...
Guardado en:
| Autores principales: | , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00062960_v47_n36_p9416_Capece |
| Aporte de: |
| id |
todo:paper_00062960_v47_n36_p9416_Capece |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_00062960_v47_n36_p9416_Capece2023-10-03T14:04:28Z Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition Capece, L. Estrin, D.A. Marti, M.A. Biochemistry Computational methods Computer networks Computer simulation Mammals Mechanisms Nitric oxide Oxygen Proteins Activation mechanisms Soluble guanylate cyclase Hemoglobin guanylate cyclase hemoprotein histidine allosterism article computer simulation enzyme activation heme nitric oxide oxygen binding ligand binding priority journal protein conformation protein domain protein structure spectroscopy Thermoanaerobacter thermoanaerobacter tencogensis Allosteric Regulation Animals Bacterial Proteins Computer Simulation Enzyme Activation Guanylate Cyclase Heme Histidine Humans Iron Models, Molecular Nitric Oxide Oxygen Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Signal Transduction Structure-Activity Relationship Thermoanaerobacter Mammalia Prokaryota Thermoanaerobacter Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO), numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO-induced breaking of the iron proximal histidine bond in the so-called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came, however, from the elucidation of crystal structures for two different prokaryotic heme NO oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX that complement these structural studies, yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the αFβ1 loop and the αA-αC distal subdomain. The results from the sGC models also support this view and suggest a key role for the αFβ1 loop in the iron proximal histidine bond breaking process and, therefore, in the sGC activation mechanism. © 2008 American Chemical Society. Fil:Capece, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00062960_v47_n36_p9416_Capece |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Biochemistry Computational methods Computer networks Computer simulation Mammals Mechanisms Nitric oxide Oxygen Proteins Activation mechanisms Soluble guanylate cyclase Hemoglobin guanylate cyclase hemoprotein histidine allosterism article computer simulation enzyme activation heme nitric oxide oxygen binding ligand binding priority journal protein conformation protein domain protein structure spectroscopy Thermoanaerobacter thermoanaerobacter tencogensis Allosteric Regulation Animals Bacterial Proteins Computer Simulation Enzyme Activation Guanylate Cyclase Heme Histidine Humans Iron Models, Molecular Nitric Oxide Oxygen Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Signal Transduction Structure-Activity Relationship Thermoanaerobacter Mammalia Prokaryota Thermoanaerobacter |
| spellingShingle |
Biochemistry Computational methods Computer networks Computer simulation Mammals Mechanisms Nitric oxide Oxygen Proteins Activation mechanisms Soluble guanylate cyclase Hemoglobin guanylate cyclase hemoprotein histidine allosterism article computer simulation enzyme activation heme nitric oxide oxygen binding ligand binding priority journal protein conformation protein domain protein structure spectroscopy Thermoanaerobacter thermoanaerobacter tencogensis Allosteric Regulation Animals Bacterial Proteins Computer Simulation Enzyme Activation Guanylate Cyclase Heme Histidine Humans Iron Models, Molecular Nitric Oxide Oxygen Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Signal Transduction Structure-Activity Relationship Thermoanaerobacter Mammalia Prokaryota Thermoanaerobacter Capece, L. Estrin, D.A. Marti, M.A. Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition |
| topic_facet |
Biochemistry Computational methods Computer networks Computer simulation Mammals Mechanisms Nitric oxide Oxygen Proteins Activation mechanisms Soluble guanylate cyclase Hemoglobin guanylate cyclase hemoprotein histidine allosterism article computer simulation enzyme activation heme nitric oxide oxygen binding ligand binding priority journal protein conformation protein domain protein structure spectroscopy Thermoanaerobacter thermoanaerobacter tencogensis Allosteric Regulation Animals Bacterial Proteins Computer Simulation Enzyme Activation Guanylate Cyclase Heme Histidine Humans Iron Models, Molecular Nitric Oxide Oxygen Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Signal Transduction Structure-Activity Relationship Thermoanaerobacter Mammalia Prokaryota Thermoanaerobacter |
| description |
Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO), numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO-induced breaking of the iron proximal histidine bond in the so-called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came, however, from the elucidation of crystal structures for two different prokaryotic heme NO oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX that complement these structural studies, yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the αFβ1 loop and the αA-αC distal subdomain. The results from the sGC models also support this view and suggest a key role for the αFβ1 loop in the iron proximal histidine bond breaking process and, therefore, in the sGC activation mechanism. © 2008 American Chemical Society. |
| format |
JOUR |
| author |
Capece, L. Estrin, D.A. Marti, M.A. |
| author_facet |
Capece, L. Estrin, D.A. Marti, M.A. |
| author_sort |
Capece, L. |
| title |
Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition |
| title_short |
Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition |
| title_full |
Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition |
| title_fullStr |
Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition |
| title_full_unstemmed |
Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition |
| title_sort |
dynamical characterization of the heme no oxygen binding (hnox) domain. insight into soluble guanylate cyclase allosteric transition |
| url |
http://hdl.handle.net/20.500.12110/paper_00062960_v47_n36_p9416_Capece |
| work_keys_str_mv |
AT capecel dynamicalcharacterizationofthehemenooxygenbindinghnoxdomaininsightintosolubleguanylatecyclaseallosterictransition AT estrinda dynamicalcharacterizationofthehemenooxygenbindinghnoxdomaininsightintosolubleguanylatecyclaseallosterictransition AT martima dynamicalcharacterizationofthehemenooxygenbindinghnoxdomaininsightintosolubleguanylatecyclaseallosterictransition |
| _version_ |
1807323573941960704 |