3n3n | pdb_00003n3n

Crystal Structure of B. pseudomallei KatG with Isonicotinic acid hydrazide bound

spinqualitylabelsall models 3n3n, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n3n is a 2 chain structure with sequence from Burkholderia pseudomallei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, HEM, MPD, NA, NIZ Related: 3n3o, 3n3p, 3n3q, 3n3r, 3n3s Gene: KatG (Burkholderia pseudomallei) Activity: Catalase, with EC number 1.11.1.6 Resources: FirstGlance, OCA, RCSB, PDBsum Function [C6TXM5_BURPS] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity (By similarity).[HAMAP-Rule:MF_01961] 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 Activation of the pro-drug isoniazid (INH) as an anti-tubercular drug in Mycobacterium tuberculosis involves its conversion to isonicotinyl-NAD, a reaction that requires the catalase-peroxidase KatG. This report shows that the reaction proceeds in the absence of KatG at a slow rate in a mixture of INH, NAD(+), Mn(2+), and O(2), and that the inclusion of KatG increases the rate by >7 times. Superoxide, generated by either Mn(2+)- or KatG-catalyzed reduction of O(2), is an essential intermediate in the reaction. Elimination of the peroxidatic process by mutation slows the rate of reaction by 60% revealing that the peroxidatic process enhances, but is not essential for isonicotinyl-NAD formation. The isonicotinyl-NAD(*+) radical is identified as a reaction intermediate, and its reduction by superoxide is proposed. Binding sites for INH and its co-substrate, NAD(+), are identified for the first time in crystal complexes of Burkholderia pseudomallei catalase-peroxidase with INH and NAD(+) grown by co-crystallization. The best defined INH binding sites were identified, one in each subunit, on the opposite side of the protein from the entrance to the heme cavity in a funnel-shaped channel. The NAD(+) binding site is approximately 20 A from the entrance to the heme cavity and involves interactions primarily with the AMP portion of the molecule in agreement with the NMR saturation transfer difference results. Isonicotinic acid hydrazide conversion to Isonicotinyl-NAD by catalase-peroxidases.,Wiseman B, Carpena X, Feliz M, Donald LJ, Pons M, Fita I, Loewen PC J Biol Chem. 2010 Aug 20;285(34):26662-73. Epub 2010 Jun 15. PMID:20554537 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Catalase

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