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1lw1

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Crystal Structure Of Mycobacterium Tuberculosis Alkylperoxidase Ahpd H137F mutant

Structural highlights

1lw1 is a 3 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] 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.^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, Ortiz De Montellano PR. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J Biol Chem. 2000 Jun 23;275(25):18801-9. PMID:10766746 doi:http://dx.doi.org/10.1074/jbc.M001001200
↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
↑ Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR. The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:12761216 doi:10.1074/jbc.M303747200
↑ Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, Ortiz De Montellano PR. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J Biol Chem. 2000 Jun 23;275(25):18801-9. PMID:10766746 doi:http://dx.doi.org/10.1074/jbc.M001001200
↑ Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science. 2002 Feb 8;295(5557):1073-7. Epub 2002 Jan 17. PMID:11799204 doi:10.1126/science.1067798
↑ Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR. The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:12761216 doi:10.1074/jbc.M303747200
↑ Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR. The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. J Biol Chem. 2003 Aug 8;278(32):29502-8. Epub 2003 May 21. PMID:12761216 doi:10.1074/jbc.M303747200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1lw1"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Djordjevic S | Nunn CM | Ortiz de Montellano PR

@@ Line 3: / Line 3: @@
 <StructureSection load='1lw1' size='340' side='right'caption='[[1lw1]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1lw1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LW1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1lw1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LW1 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gu9|1gu9]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=1lw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lw1 OCA], [https://pdbe.org/1lw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lw1 RCSB], [https://www.ebi.ac.uk/pdbsum/1lw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lw1 ProSAT]</span></td></tr>
 </table>
 == 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>
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Djordjevic, S]]
+[[Category: Djordjevic S]]
-[[Category: Montellano, P R.Ortiz de]]
+[[Category: Nunn CM]]
-[[Category: Nunn, C M]]
+[[Category: Ortiz de Montellano PR]]
-[[Category: Alkylhydroperoxidase]]
-[[Category: Oxidoreductase]]
-[[Category: Tuberculosis]]

1lw1

From Proteopedia

Current revision

Crystal Structure Of Mycobacterium Tuberculosis Alkylperoxidase Ahpd H137F mutant

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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