6hnn

Crystal structure of wild-type IdmH, a putative polyketide cyclase from Streptomyces antibioticus

spinqualitylabelsall models 6hnn, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hnn is a 10 chain structure with sequence from Streptomyces antibioticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C5HV10_STRAT Publication Abstract from PubMed Indanomycin is biosynthesized by a hybrid nonribosomal peptide synthase/polyketide synthase (NRPS/PKS) followed by a number of 'tailoring' steps to form the two ring systems that are present in the mature product. It had previously been hypothesized that the indane ring of indanomycin was formed by the action of IdmH using a Diels-Alder reaction. Here, the crystal structure of a selenomethionine-labelled truncated form of IdmH (IdmH-Delta99-107) was solved using single-wavelength anomalous dispersion (SAD) phasing. This truncated variant allows consistent and easy crystallization, but importantly the structure was used as a search model in molecular replacement, allowing the full-length IdmH structure to be determined to 2.7 A resolution. IdmH is a homodimer, with the individual protomers consisting of an alpha+beta barrel. Each protomer contains a deep hydrophobic pocket which is proposed to constitute the active site of the enzyme. To investigate the reaction catalysed by IdmH, 88% of the backbone NMR resonances were assigned, and using chemical shift perturbation of [(15)N]-labelled IdmH it was demonstrated that indanomycin binds in the active-site pocket. Finally, combined quantum mechanical/molecular mechanical (QM/MM) modelling of the IdmH reaction shows that the active site of the enzyme provides an appropriate environment to promote indane-ring formation, supporting the assignment of IdmH as the key Diels-Alderase catalysing the final step in the biosynthesis of indanomycin through a similar mechanism to other recently characterized Diels-Alderases involved in polyketide-tailoring reactions. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at https://proteopedia.org/w/Journal:IUCrJ:S2052252519012399. Crystal structure of the putative cyclase IdmH from the indanomycin nonribosomal peptide synthase/polyketide synthase.,Drulyte I, Obajdin J, Trinh CH, Kalverda AP, van der Kamp MW, Hemsworth GR, Berry A IUCrJ. 2019 Oct 24;6(Pt 6):1120-1133. doi: 10.1107/S2052252519012399. eCollection, 2019 Nov 1. PMID:31709067 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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