7x32 | pdb_00007x32

Crystal structure of E. coli NfsB in complex with berberine

spinqualitylabelsall models 7x32, resolution 1.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x32 is a 8 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.829Å Ligands: BER, DMS, FMN, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A094VLP5_ECOLX Publication Abstract from PubMed The bacterial nitroreductases (NRs) NfsB and NfsA are conserved homodimeric FMN-dependent flavoproteins that are responsible for the reduction of nitroaromatic substrates. Berberine (BBR) is a plant-derived isoquinoline alkaloid with a large conjugated ring system that is widely used in the treatment of various diseases. It was recently found that the gut microbiota convert BBR into dihydroberberine (dhBBR, the absorbable form) mediated by bacterial NRs. The molecular basis for the transformation of BBR by the gut microbiota remains unclear. Here, kinetic studies showed that NfsB from Escherichia coli (EcNfsB), rather than EcNfsA, is responsible for the conversion of BBR to dhBBR in spite of a low reaction rate. The crystal structure of the EcNfsB-BBR complex showed that BBR binds into the active pocket at the dimer interface, and its large conjugated plane stacks above the plane of the FMN cofactor in a nearly parallel orientation. BBR is mainly stabilized by pi-stacking interactions with both neighboring aromatic residues and FMN. Structure-based mutagenesis studies further revealed that the highly conserved Phe70 and Phe199 are important residues for the conversion of BBR. The structure revealed that the C6 atom of BBR (which receives the hydride) is approximately 7.5 A from the N5 atom of FMN (which donates the hydride), which is too distant for hydride transfer. Notably, several well ordered water molecules make hydrogen-bond/van der Waals contacts with the N1 atom of BBR in the active site, which probably donate protons in conjunction with electron transfer from FMN. The structure-function studies revealed the mechanism for the recognition and binding of BBR by bacterial NRs and may help to understand the conversion of BBR by the gut microbiota. Structural basis for the transformation of the traditional medicine berberine by bacterial nitroreductase.,Wen HY, Pan LB, Ma SR, Yang XY, Hu JC, Zhao HF, Gao ZQ, Dong YH, Wang Y, Zhang H Acta Crystallogr D Struct Biol. 2022 Oct 1;78(Pt 10):1273-1282. doi:, 10.1107/S2059798322008373. Epub 2022 Sep 27. PMID:36189746 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nitroreductase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA