1x7u

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{{STRUCTURE_1x7u| PDB=1x7u | SCENE= }}
{{STRUCTURE_1x7u| PDB=1x7u | SCENE= }}
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'''Crystal structure of the S324T of catalase-peroxidase KatG'''
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===Crystal structure of the S324T of catalase-peroxidase KatG===
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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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The line below this paragraph, {{ABSTRACT_PUBMED_15567407}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15567407 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15567407}}
==About this Structure==
==About this Structure==
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[[Category: Catalase-peroxidase]]
[[Category: Catalase-peroxidase]]
[[Category: Inh resistant variant]]
[[Category: Inh resistant variant]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:40:48 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:00:27 2008''

Revision as of 17:00, 27 July 2008

Image:1x7u.png

Template:STRUCTURE 1x7u

Crystal structure of the S324T of catalase-peroxidase KatG

Template:ABSTRACT PUBMED 15567407

About this Structure

1X7U is a Single protein structure of sequence from Burkholderia pseudomallei. Full crystallographic information is available from OCA.

Reference

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:15567407

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