3R5Z

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

Summary for 3R5Z

• Entry DOI: 10.2210/pdb3r5z/pdb
• Related: 3H96 3R5L 3R5P 3R5R 3R5W 3R5Y
• Descriptor: Putative uncharacterized protein, COENZYME F420, SULFATE ION, ... (4 entities in total)
• Functional Keywords: split barrel-like fold, duf385, deazaflavin-dependent reductase, f420-dependent reductase, fdr, f420, unknown function
• Biological source: Nocardia farcinica
• Total number of polymer chains: 2
• Total formula weight: 34307.84

Authors

Cellitti, S.E.,Shaffer, J.,Jones, D.H.,Mukherjee, T.,Gurumurthy, M.,Bursulaya, B.,Boshoff, H.I.M.,Choi, I.,Nayya, A.,Lee, Y.S.,Cherian, J.,Niyomrattanakit, P.,Dick, T.,Manjunatha, U.H.,Barry, C.E.,Spraggon, G.,Geierstanger, B.H. (deposition date: 2011-03-20, release date: 2012-01-18, Last modification date: 2023-09-13)

Primary citation

Cellitti, S.E.,Shaffer, J.,Jones, D.H.,Mukherjee, T.,Gurumurthy, M.,Bursulaya, B.,Boshoff, H.I.,Choi, I.,Nayyar, A.,Lee, Y.S.,Cherian, J.,Niyomrattanakit, P.,Dick, T.,Manjunatha, U.H.,Barry, C.E.,Spraggon, G.,Geierstanger, B.H.
Structure of Ddn, the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis involved in bioreductive activation of PA-824.
Structure, 20:101-112, 2012

PubMed 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.

PubMed: 22244759
DOI: 10.1016/j.str.2011.11.001

Experimental method

X-RAY DIFFRACTION (1.503 Å)