5f5l

The structure of monooxygenase KstA11 in the biosynthetic pathway of kosinostatin

spinqualitylabelsall models 5f5l, resolution 1.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5f5l is a 1 chain structure with sequence from Micromonospora sp. TP-A0468. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.68Å Ligands: DTT, GOL, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A023GUL3_9ACTN Publication Abstract from PubMed Ranking among the most effective anticancer drugs, anthracyclines represent an important family of aromatic polyketides generated by type II polyketide synthases (PKSs). After formation of polyketide cores, the post-PKS tailoring modifications endow the scaffold with various structural diversities and biological activities. Here we demonstrate an unprecedented four-enzyme-participated hydroxyl regioisomerization process involved in the biosynthesis of kosinostatin. First, KstA15 and KstA16 function together to catalyze a cryptic hydroxylation of the 4-hydroxyl-anthraquinone core, yielding a 1,4-dihydroxyl product, which undergoes a chemically challenging asymmetric reduction-dearomatization subsequently acted by KstA11; then, KstA10 catalyzes a region-specific reduction concomitant with dehydration to afford the 1-hydroxyl anthraquinone. Remarkably, the shunt product identifications of both hydroxylation and reduction-dehydration reactions, the crystal structure of KstA11 with bound substrate and cofactor, and isotope incorporation experiments reveal mechanistic insights into the redox dearomatization and rearomatization steps. These findings provide a distinguished tailoring paradigm for type II PKS engineering. Hydroxyl regioisomerization of anthracycline catalyzed by a four-enzyme cascade.,Zhang Z, Gong YK, Zhou Q, Hu Y, Ma HM, Chen YS, Igarashi Y, Pan L, Tang GL Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1554-1559. doi:, 10.1073/pnas.1610097114. Epub 2017 Jan 30. PMID:28137838 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monooxygenase 3D structures

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