3sk2

Crystal structure of phenazine resistance protein EhpR from Enterobacter agglomerans (Erwinia herbicola, Pantoea agglomerans) Eh1087 in complex with griseoluteic acid

spinqualitylabelsall models 3sk2, resolution 1.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3sk2 is a 2 chain structure with sequence from "bacillus_milletiae"_kawakami_and_yoshida_1920 "bacillus milletiae" kawakami and yoshida 1920. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GRI Gene: ehpR ("Bacillus milletiae" Kawakami and Yoshida 1920) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed ABSTRACT: BACKGROUND: The phenazines are redox-active secondary metabolites that a large number of bacterial strains produce and excrete into the environment. They possess antibiotic activity owing to the fact that they can reduce molecular oxygen to toxic reactive oxygen species. In order to take advantage of this activity, phenazine producers need to protect themselves against phenazine toxicity. Whereas it is believed that phenazine-producing pseudomonads possess highly active superoxide dismutases and catalases, it has recently been found that the plant-colonizing bacterium Enterobacter agglomerans expresses a small gene ehpR to render itself resistant towards D-alanyl-griseoluteic acid, the phenazine antibiotic produced by this strain. RESULTS: To understand the resistance mechanism installed by EhpR we have determined its crystal structure in the apo form at 2.15 A resolution and in complex with griseoluteic acid at 1.01 A, respectively. While EhpR shares a common fold with glyoxalase-I / bleomycin resistance proteins, the ligand binding site does not contain residues that some related proteins employ to chemically alter their substrates. Binding of the antibiotic is mediated by pi-stacking interactions of the aromatic moiety with the side chains of aromatic amino acids and by a few polar interactions. The dissociation constant KD between EhpR and griseoluteic acid was quantified as 244 +/- 45 uM by microscale thermophoresis measurements. CONCLUSIONS: The data accumulated here suggest that EhpR confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. It is tempting to speculate that EhpR acts in concert with EhpJ, a transport protein of the major facilitator superfamily that is also encoded in the phenazine biosynthesis operon of E. agglomerans. The low affinity of EhpR for griseoluteic acid may be required for its physiological function. Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin / mitomycin C resistance in other bacteria.,Yu S, Vit A, Devenish S, Mahanty HK, Itzen A, Goody RS, Blankenfeldt W BMC Struct Biol. 2011 Aug 17;11(1):33. PMID:21849072 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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