Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO posse...
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Autor*in:	Ignacio Boron [verfasserIn] Juan Pablo Bustamante [verfasserIn] Kelly S Davidge [verfasserIn] Sandip Singh [verfasserIn] Lesley AH Bowman [verfasserIn] Mariana Tinajero-Trejo [verfasserIn] Sebastián Carballal [verfasserIn] Rafael Radi [verfasserIn] Robert K Poole [verfasserIn] Kanak Dikshit [verfasserIn] Dario A Estrin [verfasserIn] Marcelo A Marti [verfasserIn] Leonardo Boechi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis

Übergeordnetes Werk:	In: F1000Research - F1000 Research Ltd, 2013, 4(2015)
Übergeordnetes Werk:	volume:4 ; year:2015

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.12688/f1000research.5921.2

Katalog-ID:	DOAJ039254186

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allfields	10.12688/f1000research.5921.2 doi (DE-627)DOAJ039254186 (DE-599)DOAJ88416c28732e42d9943da7596f3d1714 DE-627 ger DE-627 rakwb eng Ignacio Boron verfasserin aut Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved] 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis Medicine R Science Q Juan Pablo Bustamante verfasserin aut Kelly S Davidge verfasserin aut Sandip Singh verfasserin aut Lesley AH Bowman verfasserin aut Mariana Tinajero-Trejo verfasserin aut Sebastián Carballal verfasserin aut Rafael Radi verfasserin aut Robert K Poole verfasserin aut Kanak Dikshit verfasserin aut Dario A Estrin verfasserin aut Marcelo A Marti verfasserin aut Leonardo Boechi verfasserin aut In F1000Research F1000 Research Ltd, 2013 4(2015) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:4 year:2015 https://doi.org/10.12688/f1000research.5921.2 kostenfrei https://doaj.org/article/88416c28732e42d9943da7596f3d1714 kostenfrei http://f1000research.com/articles/4-22/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2015
spelling	10.12688/f1000research.5921.2 doi (DE-627)DOAJ039254186 (DE-599)DOAJ88416c28732e42d9943da7596f3d1714 DE-627 ger DE-627 rakwb eng Ignacio Boron verfasserin aut Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved] 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis Medicine R Science Q Juan Pablo Bustamante verfasserin aut Kelly S Davidge verfasserin aut Sandip Singh verfasserin aut Lesley AH Bowman verfasserin aut Mariana Tinajero-Trejo verfasserin aut Sebastián Carballal verfasserin aut Rafael Radi verfasserin aut Robert K Poole verfasserin aut Kanak Dikshit verfasserin aut Dario A Estrin verfasserin aut Marcelo A Marti verfasserin aut Leonardo Boechi verfasserin aut In F1000Research F1000 Research Ltd, 2013 4(2015) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:4 year:2015 https://doi.org/10.12688/f1000research.5921.2 kostenfrei https://doaj.org/article/88416c28732e42d9943da7596f3d1714 kostenfrei http://f1000research.com/articles/4-22/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2015
allfields_unstemmed	10.12688/f1000research.5921.2 doi (DE-627)DOAJ039254186 (DE-599)DOAJ88416c28732e42d9943da7596f3d1714 DE-627 ger DE-627 rakwb eng Ignacio Boron verfasserin aut Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved] 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis Medicine R Science Q Juan Pablo Bustamante verfasserin aut Kelly S Davidge verfasserin aut Sandip Singh verfasserin aut Lesley AH Bowman verfasserin aut Mariana Tinajero-Trejo verfasserin aut Sebastián Carballal verfasserin aut Rafael Radi verfasserin aut Robert K Poole verfasserin aut Kanak Dikshit verfasserin aut Dario A Estrin verfasserin aut Marcelo A Marti verfasserin aut Leonardo Boechi verfasserin aut In F1000Research F1000 Research Ltd, 2013 4(2015) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:4 year:2015 https://doi.org/10.12688/f1000research.5921.2 kostenfrei https://doaj.org/article/88416c28732e42d9943da7596f3d1714 kostenfrei http://f1000research.com/articles/4-22/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2015
allfieldsGer	10.12688/f1000research.5921.2 doi (DE-627)DOAJ039254186 (DE-599)DOAJ88416c28732e42d9943da7596f3d1714 DE-627 ger DE-627 rakwb eng Ignacio Boron verfasserin aut Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved] 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis Medicine R Science Q Juan Pablo Bustamante verfasserin aut Kelly S Davidge verfasserin aut Sandip Singh verfasserin aut Lesley AH Bowman verfasserin aut Mariana Tinajero-Trejo verfasserin aut Sebastián Carballal verfasserin aut Rafael Radi verfasserin aut Robert K Poole verfasserin aut Kanak Dikshit verfasserin aut Dario A Estrin verfasserin aut Marcelo A Marti verfasserin aut Leonardo Boechi verfasserin aut In F1000Research F1000 Research Ltd, 2013 4(2015) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:4 year:2015 https://doi.org/10.12688/f1000research.5921.2 kostenfrei https://doaj.org/article/88416c28732e42d9943da7596f3d1714 kostenfrei http://f1000research.com/articles/4-22/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2015
allfieldsSound	10.12688/f1000research.5921.2 doi (DE-627)DOAJ039254186 (DE-599)DOAJ88416c28732e42d9943da7596f3d1714 DE-627 ger DE-627 rakwb eng Ignacio Boron verfasserin aut Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved] 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis Medicine R Science Q Juan Pablo Bustamante verfasserin aut Kelly S Davidge verfasserin aut Sandip Singh verfasserin aut Lesley AH Bowman verfasserin aut Mariana Tinajero-Trejo verfasserin aut Sebastián Carballal verfasserin aut Rafael Radi verfasserin aut Robert K Poole verfasserin aut Kanak Dikshit verfasserin aut Dario A Estrin verfasserin aut Marcelo A Marti verfasserin aut Leonardo Boechi verfasserin aut In F1000Research F1000 Research Ltd, 2013 4(2015) (DE-627)735133581 (DE-600)2699932-8 20461402 nnns volume:4 year:2015 https://doi.org/10.12688/f1000research.5921.2 kostenfrei https://doaj.org/article/88416c28732e42d9943da7596f3d1714 kostenfrei http://f1000research.com/articles/4-22/v2 kostenfrei https://doaj.org/toc/2046-1402 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2015
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author	Ignacio Boron
spellingShingle	Ignacio Boron misc Biomacromolecule-Ligand Interactions misc Cellular Microbiology & Pathogenesis misc Medicine misc R misc Science misc Q Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]
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topic_title	Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved] Biomacromolecule-Ligand Interactions Cellular Microbiology & Pathogenesis
topic	misc Biomacromolecule-Ligand Interactions misc Cellular Microbiology & Pathogenesis misc Medicine misc R misc Science misc Q
topic_unstemmed	misc Biomacromolecule-Ligand Interactions misc Cellular Microbiology & Pathogenesis misc Medicine misc R misc Science misc Q
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title	Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]
ctrlnum	(DE-627)DOAJ039254186 (DE-599)DOAJ88416c28732e42d9943da7596f3d1714
title_full	Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]
author_sort	Ignacio Boron
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author_browse	Ignacio Boron Juan Pablo Bustamante Kelly S Davidge Sandip Singh Lesley AH Bowman Mariana Tinajero-Trejo Sebastián Carballal Rafael Radi Robert K Poole Kanak Dikshit Dario A Estrin Marcelo A Marti Leonardo Boechi
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title_sort	ligand uptake in mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]
title_auth	Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]
abstract	Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.
abstractGer	Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.
abstract_unstemmed	Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.
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title_short	Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]
url	https://doi.org/10.12688/f1000research.5921.2 https://doaj.org/article/88416c28732e42d9943da7596f3d1714 http://f1000research.com/articles/4-22/v2 https://doaj.org/toc/2046-1402
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author2	Juan Pablo Bustamante Kelly S Davidge Sandip Singh Lesley AH Bowman Mariana Tinajero-Trejo Sebastián Carballal Rafael Radi Robert K Poole Kanak Dikshit Dario A Estrin Marcelo A Marti Leonardo Boechi
author2Str	Juan Pablo Bustamante Kelly S Davidge Sandip Singh Lesley AH Bowman Mariana Tinajero-Trejo Sebastián Carballal Rafael Radi Robert K Poole Kanak Dikshit Dario A Estrin Marcelo A Marti Leonardo Boechi
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doi_str	10.12688/f1000research.5921.2
up_date	2024-07-03T22:26:16.830Z
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Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules [version 2; referees: 2 approved]

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