1me5
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='1me5' size='340' side='right'caption='[[1me5]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='1me5' size='340' side='right'caption='[[1me5]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1me5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[1me5]] is a 3 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=1ME5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ME5 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=1me5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1me5 OCA], [https://pdbe.org/1me5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1me5 RCSB], [https://www.ebi.ac.uk/pdbsum/1me5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1me5 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=1me5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1me5 OCA], [https://pdbe.org/1me5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1me5 RCSB], [https://www.ebi.ac.uk/pdbsum/1me5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1me5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/AHPD_MYCTU AHPD_MYCTU] Antioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity.<ref>PMID:10766746</ref> <ref>PMID:11799204</ref> <ref>PMID:12761216</ref> Together with AhpC, DlaT and Lpd, constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.<ref>PMID:10766746</ref> <ref>PMID:11799204</ref> <ref>PMID:12761216</ref> | |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 19: | Line 19: | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1me5 ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1me5 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | AhpD, a protein with two cysteine residues, is required for physiological reduction of the Mycobacterium tuberculosis alkylhydroperoxidase AhpC. AhpD also has an alkylhydroperoxidase activity of its own. The AhpC/AhpD system provides critical antioxidant protection, particularly in the absence of the catalase-peroxidase KatG, which is suppressed in most isoniazid-resistant strains. Based on the crystal structure, we proposed recently a catalytic mechanism for AhpD involving a proton relay in which the Glu118 carboxylate group, via His137 and a water molecule, deprotonates the catalytic residue Cys133 (Nunn, C. M., Djordjevic, S., Hillas, P. J., Nishida, C., and Ortiz de Montellano, P. R. (2002) J. Biol. Chem. 277, 20033-20040). A possible role for His132 in subsequent formation of the Cys133-Cys130 disulfide bond was also noted. To test this proposed mechanism, we have expressed the H137F, H137Q, H132F, H132Q, E118F, E118Q, C133S, and C130S mutants of AhpD, determined the crystal structures of the H137F and H132Q mutants, estimated the pKa values of the cysteine residues, and defined the kinetic properties of the mutant proteins. The collective results strongly support the proposed catalytic mechanism for AhpD. | ||
| - | |||
| - | The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics.,Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:12761216<ref>PMID:12761216</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1me5" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 33: | Line 24: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: | + | [[Category: Djordjevic S]] |
| - | [[Category: Nunn | + | [[Category: Nunn CM]] |
| - | [[Category: | + | [[Category: Ortiz de Montellano PR]] |
| - | + | ||
| - | + | ||
Current revision
Crystal Structure of Mycobacterium Tuberculosis Alkylperoxidase AhpD H132Q Mutant
| |||||||||||
