3R5Z: Structure of a Deazaflavin-dependent reductase from Nocardia farcinica, with co-factor F420

Citation:
Abstract
Tuberculosis continues to be a global health threat, making bicyclic nitroimidazoles an important new class of therapeutics. A deazaflavin-dependent nitroreductase (Ddn) from Mycobacterium tuberculosis catalyzes the reduction of nitroimidazoles such as PA-824, resulting in intracellular release of lethal reactive nitrogen species. The N-terminal 30 residues of Ddn are functionally important but are flexible or access multiple conformations, preventing structural characterization of the full-length, enzymatically active enzyme. Several structures were determined of a truncated, inactive Ddn protein core with and without bound F(420) deazaflavin coenzyme as well as of a catalytically competent homolog from Nocardia farcinica. Mutagenesis studies based on these structures identified residues important for binding of F(420) and PA-824. The proposed orientation of the tail of PA-824 toward the N terminus of Ddn is consistent with current structure-activity relationship data.
PDB ID: 3R5ZDownload
MMDB ID: 96515
PDB Deposition Date: 2011/3/20
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.503  Å
Source Organism:
Similar Structures:
Biological Unit for 3R5Z: monomeric; determined by author
Molecular Components in 3R5Z
Label Count Molecule
Protein (1 molecule)
1
Putative Uncharacterized Protein
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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