7bsx

SDR protein NapW-NADP

spinqualitylabelsall models 7bsx, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bsx is a 8 chain structure with sequence from Streptomyces lusitanus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S4TKM8_9ACTN Publication Abstract from PubMed Antibiotic resistance is becoming one of the major crises, among which hydrolysis reaction is widely employed by bacteria to destroy the reactive pharmacophore. Correspondingly, antibiotic producer has canonically co-evolved this approach with the biosynthetic capability for self-resistance. Here we discover a self-defense strategy featuring with reductive inactivation of hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and homW, which are integrated with the naphthyridinomycin biosynthetic pathway. We determine the crystal structure of NapW.NADPH complex and propose a catalytic mechanism by molecular dynamics simulation analysis. Additionally, a similar detoxification strategy is identified in the biosynthesis of saframycin A, another member of tetrahydroisoquinoline (THIQ) antibiotics. Remarkably, similar SDRs are widely spread in bacteria and able to inactive other THIQ members including the clinical anticancer drug, ET-743. These findings not only fill in the missing intracellular events of temporal-spatial shielding mode for cryptic self-resistance during THIQs biosynthesis, but also exhibit a sophisticated damage-control in secondary metabolism and general immunity toward this family of antibiotics. Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics.,Wen WH, Zhang Y, Zhang YY, Yu Q, Jiang CC, Tang MC, Pu JY, Wu L, Zhao YL, Shi T, Zhou J, Tang GL Nat Commun. 2021 Dec 6;12(1):7085. doi: 10.1038/s41467-021-27404-3. PMID:34873166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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