The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin
Flavohemoglobins (FHbs) are members of the globin superfamily, widely distributed among prokaryotes and eukaryotes that have been shown to carry out nitric oxide dioxygenase (NOD) activity. In prokaryotes, such as Escherichia coli, NOD activity is a defence mechanism against the NO release by the ma...
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2013
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01620134_v119_n_p75_Ferreiro http://hdl.handle.net/20.500.12110/paper_01620134_v119_n_p75_Ferreiro |
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paper:paper_01620134_v119_n_p75_Ferreiro2023-06-08T15:13:35Z The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin Ferreiro, Dardo N. Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián Flavohemoglobin Molecular dynamics Oxygen stabilization Protein electron transfer cytochrome b5 reductase dioxygenase flavohemoglobin hemoglobin derivative hemoprotein leghemoglobin ligand oxygen truncated hemoglobin unclassified drug water article computer simulation crystal structure dissociation electron transport enzyme active site enzyme activity Escherichia coli hydrogen bond hydrophobicity ligand binding oxidation reduction potential protein function protein structure proton transport structure activity relation Biocatalysis Catalytic Domain Computer Simulation Electron-Transferring Flavoproteins Electrons Escherichia coli Escherichia coli Proteins Hemoglobins Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Kinetics Ligands Models, Molecular NAD Nitric Oxide Oxygen Oxygenases Structure-Activity Relationship Thermodynamics Water Escherichia coli Eukaryota Prokaryota Flavohemoglobins (FHbs) are members of the globin superfamily, widely distributed among prokaryotes and eukaryotes that have been shown to carry out nitric oxide dioxygenase (NOD) activity. In prokaryotes, such as Escherichia coli, NOD activity is a defence mechanism against the NO release by the macrophages of the hosts' immune system during infection. Because of that, FHbs have been studied thoroughly and several drugs have been developed in an effort to fight infectious processes. Nevertheless, the protein's structural determinants involved in the NOD activity are still poorly understood. In this context, the aim of the present work is to unravel the molecular basis of FHbs structural dynamics-to-function relationship using state of the art computer simulation tools. In an effort to fulfill this goal, we studied three key processes that determine NOD activity, namely i) ligand migration into the active site ii) stabilization of the coordinated oxygen and iii) intra-protein electron transfer (ET). Our results allowed us to determine key factors related to all three processes like the presence of a long hydrophobic tunnel for ligand migration, the presence of a water mediated hydrogen bond to stabilize the coordinated oxygen and therefore achieve a high affinity, and the best possible ET paths between the FAD and the heme, where water molecules play an important role. Taken together the presented results close an important gap in our understanding of the wide and diverse globin structural-functional relationships. © 2012 Elsevier Inc. All rights reserved. Fil:Ferreiro, D.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Boechi, 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:Martí, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01620134_v119_n_p75_Ferreiro http://hdl.handle.net/20.500.12110/paper_01620134_v119_n_p75_Ferreiro |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Flavohemoglobin Molecular dynamics Oxygen stabilization Protein electron transfer cytochrome b5 reductase dioxygenase flavohemoglobin hemoglobin derivative hemoprotein leghemoglobin ligand oxygen truncated hemoglobin unclassified drug water article computer simulation crystal structure dissociation electron transport enzyme active site enzyme activity Escherichia coli hydrogen bond hydrophobicity ligand binding oxidation reduction potential protein function protein structure proton transport structure activity relation Biocatalysis Catalytic Domain Computer Simulation Electron-Transferring Flavoproteins Electrons Escherichia coli Escherichia coli Proteins Hemoglobins Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Kinetics Ligands Models, Molecular NAD Nitric Oxide Oxygen Oxygenases Structure-Activity Relationship Thermodynamics Water Escherichia coli Eukaryota Prokaryota |
| spellingShingle |
Flavohemoglobin Molecular dynamics Oxygen stabilization Protein electron transfer cytochrome b5 reductase dioxygenase flavohemoglobin hemoglobin derivative hemoprotein leghemoglobin ligand oxygen truncated hemoglobin unclassified drug water article computer simulation crystal structure dissociation electron transport enzyme active site enzyme activity Escherichia coli hydrogen bond hydrophobicity ligand binding oxidation reduction potential protein function protein structure proton transport structure activity relation Biocatalysis Catalytic Domain Computer Simulation Electron-Transferring Flavoproteins Electrons Escherichia coli Escherichia coli Proteins Hemoglobins Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Kinetics Ligands Models, Molecular NAD Nitric Oxide Oxygen Oxygenases Structure-Activity Relationship Thermodynamics Water Escherichia coli Eukaryota Prokaryota Ferreiro, Dardo N. Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin |
| topic_facet |
Flavohemoglobin Molecular dynamics Oxygen stabilization Protein electron transfer cytochrome b5 reductase dioxygenase flavohemoglobin hemoglobin derivative hemoprotein leghemoglobin ligand oxygen truncated hemoglobin unclassified drug water article computer simulation crystal structure dissociation electron transport enzyme active site enzyme activity Escherichia coli hydrogen bond hydrophobicity ligand binding oxidation reduction potential protein function protein structure proton transport structure activity relation Biocatalysis Catalytic Domain Computer Simulation Electron-Transferring Flavoproteins Electrons Escherichia coli Escherichia coli Proteins Hemoglobins Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Kinetics Ligands Models, Molecular NAD Nitric Oxide Oxygen Oxygenases Structure-Activity Relationship Thermodynamics Water Escherichia coli Eukaryota Prokaryota |
| description |
Flavohemoglobins (FHbs) are members of the globin superfamily, widely distributed among prokaryotes and eukaryotes that have been shown to carry out nitric oxide dioxygenase (NOD) activity. In prokaryotes, such as Escherichia coli, NOD activity is a defence mechanism against the NO release by the macrophages of the hosts' immune system during infection. Because of that, FHbs have been studied thoroughly and several drugs have been developed in an effort to fight infectious processes. Nevertheless, the protein's structural determinants involved in the NOD activity are still poorly understood. In this context, the aim of the present work is to unravel the molecular basis of FHbs structural dynamics-to-function relationship using state of the art computer simulation tools. In an effort to fulfill this goal, we studied three key processes that determine NOD activity, namely i) ligand migration into the active site ii) stabilization of the coordinated oxygen and iii) intra-protein electron transfer (ET). Our results allowed us to determine key factors related to all three processes like the presence of a long hydrophobic tunnel for ligand migration, the presence of a water mediated hydrogen bond to stabilize the coordinated oxygen and therefore achieve a high affinity, and the best possible ET paths between the FAD and the heme, where water molecules play an important role. Taken together the presented results close an important gap in our understanding of the wide and diverse globin structural-functional relationships. © 2012 Elsevier Inc. All rights reserved. |
| author |
Ferreiro, Dardo N. Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián |
| author_facet |
Ferreiro, Dardo N. Boechi, Leonardo Estrin, Dario Ariel Martí, Marcelo Adrián |
| author_sort |
Ferreiro, Dardo N. |
| title |
The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin |
| title_short |
The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin |
| title_full |
The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin |
| title_fullStr |
The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin |
| title_full_unstemmed |
The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin |
| title_sort |
key role of water in the dioxygenase function of escherichia coli flavohemoglobin |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01620134_v119_n_p75_Ferreiro http://hdl.handle.net/20.500.12110/paper_01620134_v119_n_p75_Ferreiro |
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