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| - | [[Image:1x7u.jpg|left|200px]]<br /><applet load="1x7u" size="350" color="white" frame="true" align="right" spinBox="true" | + | #REDIRECT [[5l02]] This PDB entry is obsolete and replaced by 5l02 |
| - | caption="1x7u, resolution 1.90Å" />
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| - | '''Crystal structure of the S324T of catalase-peroxidase KatG'''<br />
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| - | ==Overview==
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| - | The Ser315Thr variant of the catalase-peroxidase KatG from Mycobacterium tuberculosis imparts resistance to the pro-drug isonicotinic acid hydrazide (isoniazid) through a failure to convert it to the active drug, isonicotinoyl-NAD. The equivalent variant in KatG from Burkholderia pseudomallei, Ser324Thr, has been constructed, revealing catalase and peroxidase activities that are similar to those of the native enzyme. The other activities of the variant protein, including the NADH oxidase, the isoniazid hydrazinolysis and isonicotinoyl-NAD synthase activities are reduced by 60-70%. The crystal structure of the variant differs from that of the native enzyme in having the methyl group of Thr324 situated in the entrance channel to the heme cavity, in a modified water matrix in the entrance channel and heme cavity, in lacking the putative perhydroxy modification on the heme, in the multiple locations of a few side-chains, and in the presence of an apparent perhydroxy modification on the indole nitrogen atom of the active-site Trp111. The position of the methyl group of Thr324 creates a constriction or narrowing of the channel leading to the heme cavity, providing an explanation for the lower reactivity towards isoniazid and the slower rate of isonicotinoyl-NAD synthesis.
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| - | ==About this Structure==
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| - | 1X7U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=HEM:'>HEM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X7U OCA].
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| - | ==Reference==
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| - | Structural characterization of the Ser324Thr variant of the catalase-peroxidase (KatG) from Burkholderia pseudomallei., Deemagarn T, Carpena X, Singh R, Wiseman B, Fita I, Loewen PC, J Mol Biol. 2005 Jan 7;345(1):21-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15567407 15567407]
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| - | [[Category: Burkholderia pseudomallei]]
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| - | [[Category: Catalase]]
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| - | [[Category: Single protein]]
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| - | [[Category: Carpena, X.]]
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| - | [[Category: Deemagarn, T.]]
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| - | [[Category: Fita, I.]]
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| - | [[Category: Loewen, P C.]]
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| - | [[Category: Singh, R.]]
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| - | [[Category: Wiseman, B.]]
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| - | [[Category: HEM]]
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| - | [[Category: NA]]
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| - | [[Category: catalase-peroxidase]]
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| - | [[Category: inh resistant variant]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:51:59 2008''
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