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| | ==High resolution X-ray structure of the N-terminal truncated form (residues 1-11) of Mycobacterium tuberculosis HbN== | | ==High resolution X-ray structure of the N-terminal truncated form (residues 1-11) of Mycobacterium tuberculosis HbN== |
| - | <StructureSection load='5ab8' size='340' side='right' caption='[[5ab8]], [[Resolution|resolution]] 1.53Å' scene=''> | + | <StructureSection load='5ab8' size='340' side='right'caption='[[5ab8]], [[Resolution|resolution]] 1.53Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ab8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AB8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AB8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ab8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AB8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ab8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ab8 OCA], [http://pdbe.org/5ab8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ab8 RCSB], [http://www.ebi.ac.uk/pdbsum/5ab8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ab8 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ab8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ab8 OCA], [https://pdbe.org/5ab8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ab8 RCSB], [https://www.ebi.ac.uk/pdbsum/5ab8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ab8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRHBN_MYCTU TRHBN_MYCTU]] Binds oxygen cooperatively with very high affinity (P(50) = 0.013 mmHg at 20 degrees Celsius) because of a fast combination (25 microM(-1).s(-1)) and a slow dissociation (0.2 s(-1)) rate. | + | [https://www.uniprot.org/uniprot/TRHBN_MYCTU TRHBN_MYCTU] Binds oxygen cooperatively with very high affinity (P(50) = 0.013 mmHg at 20 degrees Celsius) because of a fast combination (25 microM(-1).s(-1)) and a slow dissociation (0.2 s(-1)) rate. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ascenzi, P]] | + | [[Category: Large Structures]] |
| - | [[Category: Bidon-Chanal, A]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Boechi, L]] | + | [[Category: Ascenzi P]] |
| - | [[Category: Bolognesi, M]] | + | [[Category: Bidon-Chanal A]] |
| - | [[Category: Bustamante, J P]] | + | [[Category: Boechi L]] |
| - | [[Category: Estrin, D A]] | + | [[Category: Bolognesi M]] |
| - | [[Category: Guertin, M]] | + | [[Category: Bustamante JP]] |
| - | [[Category: Luque, F J]] | + | [[Category: Estrin DA]] |
| - | [[Category: Nardini, M]] | + | [[Category: Guertin M]] |
| - | [[Category: Pesce, A]] | + | [[Category: Luque FJ]] |
| - | [[Category: Sebilo, A]] | + | [[Category: Nardini M]] |
| - | [[Category: 2/2 hemoglobin]]
| + | [[Category: Pesce A]] |
| - | [[Category: Bacterial globin]]
| + | [[Category: Sebilo A]] |
| - | [[Category: Globin dynamic]]
| + | |
| - | [[Category: Heme/ligand tunneling]]
| + | |
| - | [[Category: No dioxygenase]]
| + | |
| - | [[Category: Oxygen transport]]
| + | |
| - | [[Category: Truncated hemoglobin]]
| + | |
| Structural highlights
Function
TRHBN_MYCTU Binds oxygen cooperatively with very high affinity (P(50) = 0.013 mmHg at 20 degrees Celsius) because of a fast combination (25 microM(-1).s(-1)) and a slow dissociation (0.2 s(-1)) rate.
Publication Abstract from PubMed
A unique defense mechanisms by which Mycobacterium tuberculosis protects itself from nitrosative stress is based on the O2 -dependent NO-dioxygenase (NOD) activity of truncated hemoglobin 2/2HbN (Mt2/2HbN). The NOD activity largely depends on the efficiency of ligand migration to the heme cavity through a two-tunnel (long and short) system; recently, it was also correlated with the presence at the Mt2/2HbN N-terminus of a short pre-A region, not conserved in most 2/2HbNs, whose deletion results in a drastic reduction of NO scavenging. In the present study, we report the crystal structure of Mt2/2HbN-DeltapreA, lacking the pre-A region, at a resolution of 1.53 A. We show that removal of the pre-A region results in long range effects on the protein C-terminus, promoting the assembly of a stable dimer, both in the crystals and in solution. In the Mt2/2HbN-DeltapreA dimer, access of heme ligands to the short tunnel is hindered. Molecular dynamics simulations show that the long tunnel branch is the only accessible pathway for O2 -ligand migration to/from the heme, and that the gating residue Phe(62)E15 partly restricts the diameter of the tunnel. Accordingly, kinetic measurements indicate that the kon value for peroxynitrite isomerization by Mt2/2HbN-DeltapreA-Fe(III) is four-fold lower relative to the full-length protein, and that NO scavenging by Mt2/2HbN-DeltapreA-Fe(II)-O2 is reduced by 35-fold. Therefore, we speculate that Mt2/2HbN evolved to host the pre-A region as a mechanism for preventing dimerization, thus reinforcing the survival of the microorganism against the reactive nitrosative stress in macrophages. DATABASE: Coordinates and structure factors have been deposited in the Protein Data Bank under accession number 5AB8.
The N-terminal pre-A region of Mycobacterium tuberculosis 2/2HbN promotes NO-dioxygenase activity.,Pesce A, Bustamante JP, Bidon-Chanal A, Boechi L, Estrin DA, Luque FJ, Sebilo A, Guertin M, Bolognesi M, Ascenzi P, Nardini M FEBS J. 2016 Jan;283(2):305-22. doi: 10.1111/febs.13571. Epub 2015 Nov 16. PMID:26499089[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pesce A, Bustamante JP, Bidon-Chanal A, Boechi L, Estrin DA, Luque FJ, Sebilo A, Guertin M, Bolognesi M, Ascenzi P, Nardini M. The N-terminal pre-A region of Mycobacterium tuberculosis 2/2HbN promotes NO-dioxygenase activity. FEBS J. 2016 Jan;283(2):305-22. doi: 10.1111/febs.13571. Epub 2015 Nov 16. PMID:26499089 doi:http://dx.doi.org/10.1111/febs.13571
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