5L02

S324T variant of B. pseudomallei KatG

Replaces:  1X7U

Summary for 5L02

• Entry DOI: 10.2210/pdb5l02/pdb
• Related: 1X7U
• Descriptor: Catalase-peroxidase, PROTOPORPHYRIN IX CONTAINING FE, SODIUM ION, ... (6 entities in total)
• Functional Keywords: catalase, peroxidase, katg, s324t variant, oxidoreductase
• Biological source: Burkholderia pseudomallei (strain 1710b)
• Total number of polymer chains: 2
• Total formula weight: 160989.43

Authors

Loewen, P.C. (deposition date: 2016-07-26, release date: 2016-08-10, Last modification date: 2023-11-15)

Primary citation

Deemagarn, T.,Carpena, X.,Singh, R.,Wiseman, B.,Fita, I.,Loewen, P.C.
Structural characterization of the Ser324Thr variant of the catalase-peroxidase (KatG) from Burkholderia pseudomallei
J. Mol. Biol., 345:21-28, 2005

PubMed Abstract: 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.

PubMed: 15567407

Experimental method

X-RAY DIFFRACTION (1.9 Å)