Summary for 5SYI
| Entry DOI | 10.2210/pdb5syi/pdb |
| Related | 5L02 5L05 5SW4 5SW5 5SW6 5SX0 5SX1 5SX2 5SX3 5SX6 5SX7 5SXQ 5SXR 5SXS 5SXT 5SXX 5SYH 5SYJ 5SYK 5SYL 5SYU 5SYV 5SYW 5SYX 5SYY |
| Descriptor | Catalase-peroxidase, PROTOPORPHYRIN IX CONTAINING FE, SODIUM ION, ... (9 entities in total) |
| Functional Keywords | catalase-peroxidase, katg, isoniazid, d141a variant, oxidoreductase |
| Biological source | Burkholderia pseudomallei (strain 1710b) |
| Total number of polymer chains | 2 |
| Total formula weight | 161473.87 |
| Authors | Loewen, P.C. (deposition date: 2016-08-11, release date: 2016-09-07, Last modification date: 2024-10-23) |
| Primary citation | Vidossich, P.,Loewen, P.C.,Carpena, X.,Fiorin, G.,Fita, I.,Rovira, C. Binding of the antitubercular pro-drug isoniazid in the heme access channel of catalase-peroxidase (KatG). A combined structural and metadynamics investigation. J Phys Chem B, 118:2924-2931, 2014 Cited by PubMed Abstract: 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. PubMed: 24568093DOI: 10.1021/jp4123425 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
Download full validation report
