5syj | pdb_00005syj

Crystal structure of the D141A variant of B. pseudomallei KatGin complex with isoniazid

spinqualitylabelsall models 5syj, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5syj is a 2 chain structure with sequence from Burkholderia pseudomallei 1710b. This structure supersedes the now removed PDB entry 4kwq. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.88Å Ligands: CL, HEM, MPD, NA, NIZ, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KATG_BURP1 Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Publication Abstract from PubMed Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD, by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel. Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation.,Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Catalase 3D structures

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