Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues
The crystallographic structure of oxygenated trHbN from Mycobacterium tuberculosis showed an extended heme distal site hydrogen-bonding network that includes Y(B10), Q(E11), and the bound O-2 (Milani, M., et al. (2001) EMBO J. 20, 3902-3909). In the present work, we analyze the effects that substitu...
Published in: | Biochemistry |
---|---|
Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
American Chemical Society
2006
|
Subjects: | |
Online Access: | http://hdl.handle.net/2434/62672 https://doi.org/10.1021/bi060112o |
id |
ftunivmilanoair:oai:air.unimi.it:2434/62672 |
---|---|
record_format |
openpolar |
spelling |
ftunivmilanoair:oai:air.unimi.it:2434/62672 2024-04-21T08:12:22+00:00 Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues Y. Ouellet M. Milani M. Couture M. Guertin M. Bolognesi Y. Ouellet M. Milani M. Couture M. Bolognesi M. Guertin 2006-07-25 http://hdl.handle.net/2434/62672 https://doi.org/10.1021/bi060112o eng eng American Chemical Society info:eu-repo/semantics/altIdentifier/pmid/16846220 info:eu-repo/semantics/altIdentifier/wos/WOS:000239086000008 volume:45 issue:29 firstpage:8770 lastpage:8781 journal:BIOCHEMISTRY http://hdl.handle.net/2434/62672 doi:10.1021/bi060112o info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-33746224034 sperm-whale myoglobin nitric-oxide synthase hydrogen-bond network resonance raman lucina-pectinata cyanide binding o-2 affinity Settore BIO/10 - Biochimica info:eu-repo/semantics/article 2006 ftunivmilanoair https://doi.org/10.1021/bi060112o 2024-03-27T16:25:40Z The crystallographic structure of oxygenated trHbN from Mycobacterium tuberculosis showed an extended heme distal site hydrogen-bonding network that includes Y(B10), Q(E11), and the bound O-2 (Milani, M., et al. (2001) EMBO J. 20, 3902-3909). In the present work, we analyze the effects that substitutions at the B10 and E11 positions exert on the heme and its coordinated ligands, using steady-state resonance Raman spectroscopy, absorption spectroscopy and X-ray crystallography. Our results show that (1) residues Y(B10) and Q(E11) control the binding and the ionization state of the heme-bound water molecules in ferric trHbN and are important in keeping the sixth coordination position vacant in deoxy trHbN; (2) residue Q(E11) plays a role in maintaining the integrity of the proximal Fe-His bond in deoxy trHbN; (3) in wild-type oxy-trHbN, the size and hydrogen-bonding capability of residue E11 is important to sustain proper interaction between Y(B10) and the heme-bound O-2; (4) CO-trHbN is in a conformational equilibrium, where either the Y(B10) or the Q(E11) residue interacts with the hemebound CO; and (5) Y(B10) and Q(E11) residues control the conformation (and likely the dynamics) of the protein matrix tunnel gating residue F(E15). These findings suggest that the functional processes of ligand binding and diffusion are controlled in trHbN through the dynamic interaction of residues Y(B10), Q(E11), F(E15), and the heme ligand. Article in Journal/Newspaper Sperm whale The University of Milan: Archivio Istituzionale della Ricerca (AIR) Biochemistry 45 29 8770 8781 |
institution |
Open Polar |
collection |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
op_collection_id |
ftunivmilanoair |
language |
English |
topic |
sperm-whale myoglobin nitric-oxide synthase hydrogen-bond network resonance raman lucina-pectinata cyanide binding o-2 affinity Settore BIO/10 - Biochimica |
spellingShingle |
sperm-whale myoglobin nitric-oxide synthase hydrogen-bond network resonance raman lucina-pectinata cyanide binding o-2 affinity Settore BIO/10 - Biochimica Y. Ouellet M. Milani M. Couture M. Guertin M. Bolognesi Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues |
topic_facet |
sperm-whale myoglobin nitric-oxide synthase hydrogen-bond network resonance raman lucina-pectinata cyanide binding o-2 affinity Settore BIO/10 - Biochimica |
description |
The crystallographic structure of oxygenated trHbN from Mycobacterium tuberculosis showed an extended heme distal site hydrogen-bonding network that includes Y(B10), Q(E11), and the bound O-2 (Milani, M., et al. (2001) EMBO J. 20, 3902-3909). In the present work, we analyze the effects that substitutions at the B10 and E11 positions exert on the heme and its coordinated ligands, using steady-state resonance Raman spectroscopy, absorption spectroscopy and X-ray crystallography. Our results show that (1) residues Y(B10) and Q(E11) control the binding and the ionization state of the heme-bound water molecules in ferric trHbN and are important in keeping the sixth coordination position vacant in deoxy trHbN; (2) residue Q(E11) plays a role in maintaining the integrity of the proximal Fe-His bond in deoxy trHbN; (3) in wild-type oxy-trHbN, the size and hydrogen-bonding capability of residue E11 is important to sustain proper interaction between Y(B10) and the heme-bound O-2; (4) CO-trHbN is in a conformational equilibrium, where either the Y(B10) or the Q(E11) residue interacts with the hemebound CO; and (5) Y(B10) and Q(E11) residues control the conformation (and likely the dynamics) of the protein matrix tunnel gating residue F(E15). These findings suggest that the functional processes of ligand binding and diffusion are controlled in trHbN through the dynamic interaction of residues Y(B10), Q(E11), F(E15), and the heme ligand. |
author2 |
Y. Ouellet M. Milani M. Couture M. Bolognesi M. Guertin |
format |
Article in Journal/Newspaper |
author |
Y. Ouellet M. Milani M. Couture M. Guertin M. Bolognesi |
author_facet |
Y. Ouellet M. Milani M. Couture M. Guertin M. Bolognesi |
author_sort |
Y. Ouellet |
title |
Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues |
title_short |
Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues |
title_full |
Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues |
title_fullStr |
Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues |
title_full_unstemmed |
Ligand interactions in the distal heme pocket of Mycobacterium tuberculosis truncated hemoglobin N : Roles of TyrB10 and GlnE11 residues |
title_sort |
ligand interactions in the distal heme pocket of mycobacterium tuberculosis truncated hemoglobin n : roles of tyrb10 and glne11 residues |
publisher |
American Chemical Society |
publishDate |
2006 |
url |
http://hdl.handle.net/2434/62672 https://doi.org/10.1021/bi060112o |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/16846220 info:eu-repo/semantics/altIdentifier/wos/WOS:000239086000008 volume:45 issue:29 firstpage:8770 lastpage:8781 journal:BIOCHEMISTRY http://hdl.handle.net/2434/62672 doi:10.1021/bi060112o info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-33746224034 |
op_doi |
https://doi.org/10.1021/bi060112o |
container_title |
Biochemistry |
container_volume |
45 |
container_issue |
29 |
container_start_page |
8770 |
op_container_end_page |
8781 |
_version_ |
1796932394809294848 |