This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
5ab8
From Proteopedia
(Difference between revisions)
m (Protected "5ab8" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==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=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ab8]] is a 1 chain structure. 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> | ||
| + | </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> | ||
| + | <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]</span></td></tr> | ||
| + | </table> | ||
| + | == 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:26499089</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5ab8" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Ascenzi, P]] | [[Category: Ascenzi, P]] | ||
| - | [[Category: Bustamante, J | + | [[Category: Bidon-Chanal, A]] |
| + | [[Category: Boechi, L]] | ||
| + | [[Category: Bolognesi, M]] | ||
| + | [[Category: Bustamante, J P]] | ||
| + | [[Category: Estrin, D A]] | ||
[[Category: Guertin, M]] | [[Category: Guertin, M]] | ||
| - | [[Category: | + | [[Category: Luque, F J]] |
[[Category: Nardini, M]] | [[Category: Nardini, M]] | ||
| + | [[Category: Pesce, A]] | ||
[[Category: Sebilo, A]] | [[Category: Sebilo, A]] | ||
| - | [[Category: | + | [[Category: 2/2 hemoglobin]] |
| - | [[Category: | + | [[Category: Bacterial globin]] |
| - | [[Category: | + | [[Category: Globin dynamic]] |
| + | [[Category: Heme/ligand tunneling]] | ||
| + | [[Category: No dioxygenase]] | ||
| + | [[Category: Oxygen transport]] | ||
| + | [[Category: Truncated hemoglobin]] | ||
Revision as of 19:59, 9 March 2016
High resolution X-ray structure of the N-terminal truncated form (residues 1-11) of Mycobacterium tuberculosis HbN
| |||||||||||
