9b02

nnhA C357A catalytic mutant in tris buffer

spinqualitylabelsall models 9b02, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9b02 is a 1 chain structure with sequence from Mycobacterium sp. JS330. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.97Å Ligands: CL, DMS, EDO, GOL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NNHA_MYCS0 Publication Abstract from PubMed The antibiotic 2-nitroimidazole (2NI) or azomycin, used for treating drug-resistant tuberculosis and imaging tumor hypoxia, requires activation by bacterial nitroreductases for its antibiotic and cytotoxic effect. Mycobacterium sp. JS330 produces 2-nitroimidazole nitrohydrolase (NnhA) that circumvents 2NI activation, conferring 2NI resistance by hydrolysing it to nitrite and imidazol-2-one (IM2O) instead. This study elucidates NnhA's structure, catalytic mechanism, and evolutionary background within the guanidino-group modifying enzyme (GME) superfamily, aided by a more soluble protein variant engineered through directed evolution. Despite low sequence similarity and limited occurrence in a few soil-dwelling mycobacteria and Actinomycetota, NnhA maintains the alpha/beta propeller fold characteristic of GME superfamily enzymes and forms an unusual hexameric ring structure formed by a trimer of domain-swapped dimers. The similarity of its active site to arginine deiminases (ADIs) and human dimethylarginine dimethylaminohydrolases (DDAHs), along with molecular dynamics simulations, suggests NnhA's catalytic mechanism resembles the hydrolysis reactions of these related enzymes. Structural insights into the enzymatic breakdown of azomycin-derived antibiotics by 2-nitroimdazole hydrolase (NnhA).,Ahmed FH, Liu JW, Royan S, Warden AC, Esquirol L, Pandey G, Newman J, Scott C, Peat TS Commun Biol. 2024 Dec 19;7(1):1676. doi: 10.1038/s42003-024-07336-6. PMID:39702827 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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