6nki

Structure of PhqB Reductase Domain from Penicillium fellutanum

spinqualitylabelsall models 6nki, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nki is a 1 chain structure with sequence from Nrrl 746. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NDP Gene: phqB (NRRL 746) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Prenylated indole alkaloids such as the calmodulin-inhibitory malbrancheamides and anthelmintic paraherquamides possess great structural diversity and pharmaceutical utility. Here, we report complete elucidation of the malbrancheamide biosynthetic pathway accomplished through complementary approaches. These include a biomimetic total synthesis to access the natural alkaloid and biosynthetic intermediates in racemic form and in vitro enzymatic reconstitution to provide access to the natural antipode (+)-malbrancheamide. Reductive cleavage of an L-Pro-L-Trp dipeptide from the MalG non-ribosomal peptide synthetase (NRPS) followed by reverse prenylation and a cascade of post-NRPS reactions culminates in an intramolecular [4+2] hetero-Diels-Alder (IMDA) cyclization to furnish the bicyclo[2.2.2]diazaoctane scaffold. Enzymatic assembly of optically pure (+)-premalbrancheamide involves an unexpected zwitterionic intermediate where MalC catalyses enantioselective cycloaddition as a bifunctional NADPH-dependent reductase/Diels-Alderase. The crystal structures of substrate and product complexes together with site-directed mutagenesis and molecular dynamics simulations demonstrate how MalC and PhqE (its homologue from the paraherquamide pathway) catalyse diastereo- and enantioselective cyclization in the construction of this important class of secondary metabolites. Fungal indole alkaloid biogenesis through evolution of a bifunctional reductase/Diels-Alderase.,Dan Q, Newmister SA, Klas KR, Fraley AE, McAfoos TJ, Somoza AD, Sunderhaus JD, Ye Y, Shende VV, Yu F, Sanders JN, Brown WC, Zhao L, Paton RS, Houk KN, Smith JL, Sherman DH, Williams RM Nat Chem. 2019 Sep 23. pii: 10.1038/s41557-019-0326-6. doi:, 10.1038/s41557-019-0326-6. PMID:31548667 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA