9w5t | pdb_00009w5t

The complex structure of wild-type P450 enzyme with cww

spinqualitylabelsall models 9w5t, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9w5t is a 1 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 2.5Å Ligands: HEM, NA, UYM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Bispyrrolidinoindoline-diketopiperazines (BPI-DKP) alkaloids, characterized by a complex 3a,3a'-bispyrrolidino[2,3-b]indoline scaffold, constitute a large class of synthetically challenging bioactive pyrroloindoline natural products. Their biosynthesis, mediated by P450 enzymes, involves oxidative dimerization of diketopiperazines (DKPs), yet the underlying mechanistic and stereochemical details have remained unclear. Here, we elucidate the molecular mechanism of TtpB1, a P450 dimerase that stereoselectively couples two DKP units to form C(2)-symmetric BPI scaffolds through an unexpected cascade. Contrary to the prevailing double-radical coupling hypothesis, integrated structural, biochemical, and computational studies reveal a stepwise process: (i) Compound I-mediated generation of a nitrogen-centered DKP radical, triggering cyclization to a C3-radical pyrroloindoline intermediate; (ii) radical addition to the C3' position of a second DKP; and (iii) single-electron transfer (SET)-driven cyclization to construct the second pyrroloindoline unit. This dual N-centered radical- and SET-driven cyclization showcases unprecedented versatility in natural product dimer biosynthesis. Molecular dynamics and QM/MM calculations further demonstrate how substrate conformational dynamics enforce stereochemical fidelity, yielding the C(2)-symmetric BPI-DKP core with vicinal quaternary stereocenters. These findings provide the first structure-guided mechanistic elucidation of BPI-DKP synthase, laying the groundwork for rational enzyme engineering and biomimetic synthesis of these pharmacologically important alkaloids. P450-Mediated Dual Cyclization Mechanisms for Pyrroloindoline Unit Formation in Bispyrrolidinoindoline Diketopiperazine Alkaloid Biosynthesis.,Du Y, Wei G, Zhou TP, Dai Y, Tian W, Tang M, Deng Z, Wang B, Qu X J Am Chem Soc. 2025 Dec 10;147(49):45199-45209. doi: 10.1021/jacs.5c14741. Epub , 2025 Dec 1. PMID:41326270 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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