5K8P

Zn2+/Tetrahedral intermediate-bound R289A 5-nitroanthranilate aminohydrolase

Summary for 5K8P

• Entry DOI: 10.2210/pdb5k8p/pdb
• Related: 5K8M 5K8N 5K8O
• Descriptor: 5-nitroanthranilic acid aminohydrolase, ZINC ION, (6~{R})-6-azanyl-3-nitro-6-oxidanyl-cyclohexa-1,3-diene-1-carboxylic acid, ... (5 entities in total)
• Functional Keywords: nitroaromatics, deaminase, metalloenzyme, hydrolase
• Biological source: Bradyrhizobium sp.
• Total number of polymer chains: 8
• Total formula weight: 372976.42

Authors

Kalyoncu, S. (deposition date: 2016-05-30, release date: 2016-10-05, Last modification date: 2023-09-27)

Primary citation

Kalyoncu, S.,Heaner, D.P.,Kurt, Z.,Bethel, C.M.,Ukachukwu, C.U.,Chakravarthy, S.,Spain, J.C.,Lieberman, R.L.
Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution.
Nat.Chem.Biol., 12:1031-1036, 2016

PubMed Abstract: Nitroaromatic compounds are typically toxic and resistant to degradation. Bradyrhizobium species strain JS329 metabolizes 5-nitroanthranilic acid (5NAA), which is a molecule secreted by Streptomyces scabies, the plant pathogen responsible for potato scab. The first biodegradation enzyme is 5NAA-aminohydrolase (5NAA-A), a metalloprotease family member that converts 5NAA to 5-nitrosalicylic acid. We characterized 5NAA-A biochemically and obtained snapshots of its mechanism. 5NAA-A, an octamer that can use several divalent transition metals for catalysis in vitro, employs a nucleophilic aromatic substitution mechanism. Unexpectedly, the metal in 5NAA-A is labile but is readily loaded in the presence of substrate. 5NAA-A is specific for 5NAA and cannot hydrolyze other tested derivatives, which are likewise poor inhibitors. The 5NAA-A structure and mechanism expand our understanding of the chemical ecology of an agriculturally important plant and pathogen, and will inform bioremediation and biocatalytic approaches to mitigate the environmental and ecological impact of nitroanilines and other challenging substrates.

PubMed: 27694799
DOI: 10.1038/nchembio.2191

Experimental method

X-RAY DIFFRACTION (2.2 Å)