2cca

From Proteopedia

(Difference between revisions)

Revision as of 00:22, 12 September 2015

Crystal structure of the catalase-peroxidase (KatG) and S315T mutant from Mycobacterium tuberculosis

Structural highlights

2cca is a 2 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1sfz, 1sj2, 2cc4, 2ccd
Activity:	Catalase, with EC number 1.11.1.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[KATG_MYCTU] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid (INH) lyase and isonicotinoyl-NAD synthase activity. May play a role in the intracellular survival of mycobacteria. May be involved in DNA repair. Partly complements recA-deficient E.coli cells exposed to UV radiation, mitomycin C or hydrogen peroxide. Increases resistance to mitomycin C in E.coli cells deficient for either uvrA, uvrB or uvrC.^[1]

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

Inhibition of the enzyme Mycobacterium tuberculosis InhA (enoyl-acyl carrier protein reductase) due to formation of an isonicotinoyl-NAD adduct (IN-NAD) from isoniazid (INH) and nicotinamide adenine dinucleotide cofactor is considered central to the mode of action of INH, a first-line treatment for tuberculosis infection. INH action against mycobacteria requires catalase-peroxidase (KatG) function, and IN-NAD adduct formation is catalyzed in vitro by M. tuberculosis KatG under a variety of conditions, yet a physiologically relevant approach to the process has not emerged that allows scrutiny of the mechanism and the origins of INH resistance in the most prevalent drug-resistant strain bearing KatG[S315T]. In this report, we describe how hydrogen peroxide, delivered at very low concentrations to ferric KatG, leads to efficient inhibition of InhA due to formation of the IN-NAD adduct. The rate of adduct formation mediated by wild-type KatG was about 20-fold greater than by the isoniazid-resistant KatG[S315T] mutant under optimal conditions (H2O2 supplied along with NAD+ and INH). Slow adduct formation also occurs starting with NADH and INH, in the presence of KatG even in the absence of added peroxide, due to endogenous peroxide. The poor efficiency of the KatG[S315T] mutant can be enhanced merely by increasing the concentration of INH, consistent with this enzyme's reduced affinity for INH binding to the resting enzyme and the catalytically competent enzyme intermediate (Compound I). Origins of drug resistance in the KatG[S315T] mutant enzyme are analyzed at the structural level through examination of the three-dimensional X-ray crystal structure of the mutant enzyme.

Hydrogen peroxide-mediated isoniazid activation catalyzed by Mycobacterium tuberculosis catalase-peroxidase (KatG) and its S315T mutant.,Zhao X, Yu H, Yu S, Wang F, Sacchettini JC, Magliozzo RS Biochemistry. 2006 Apr 4;45(13):4131-40. PMID:16566587^[2]

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

References

↑ Mulder MA, Nair S, Abratt VR, Zappe H, Steyn LM. Involvement of the N- and C-terminal domains of Mycobacterium tuberculosis KatG in the protection of mutant Escherichia coli against DNA-damaging agents. Microbiology. 1999 Aug;145 ( Pt 8):2011-21. PMID:10463167
↑ Zhao X, Yu H, Yu S, Wang F, Sacchettini JC, Magliozzo RS. Hydrogen peroxide-mediated isoniazid activation catalyzed by Mycobacterium tuberculosis catalase-peroxidase (KatG) and its S315T mutant. Biochemistry. 2006 Apr 4;45(13):4131-40. PMID:16566587 doi:10.1021/bi051967o

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2cca"

@@ Line 6: / Line 6: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sfz|1sfz]], [[1sj2|1sj2]], [[2cc4|2cc4]], [[2ccd|2ccd]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase Catalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.6 1.11.1.6] </span></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=2cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cca OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2cca RCSB], [http://www.ebi.ac.uk/pdbsum/2cca PDBsum]</span></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=2cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cca OCA], [http://pdbe.org/2cca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cca RCSB], [http://www.ebi.ac.uk/pdbsum/2cca PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2cca" style="background-color:#fffaf0;"></div>
 ==See Also==

2cca

From Proteopedia

Revision as of 00:22, 12 September 2015

Crystal structure of the catalase-peroxidase (KatG) and S315T mutant from Mycobacterium tuberculosis

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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