9dqr

Crystal structure of HrmJ from Streptomyces sp. Ag109_G2-6 (HrmJ-ssa) complexed with vanadyl(IV)-oxo and succinate

spinqualitylabelsall models 9dqr, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9dqr is a 2 chain structure with sequence from Streptomyces sp. Ag109_G2-6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: SIN, VVO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A3N4ZHX0_9ACTN Publication Abstract from PubMed Despite the diversity of reactions catalyzed by mononuclear iron and 2-oxoglutarate-dependent enzymes, the factors that lead to diverse reaction outcomes beyond canonical hydroxylation remain elusive. Cyclopropanation reactions are of particular interest not only due to the prevalence of cyclopropane moieties in pharmaceuticals but also due to the chemistry that allows cyclopropanation to outcompete oxygen rebound. HrmJ is one such cyclopropanase from the biosynthetic pathway of hormaomycin; however, a homologue is herein discovered that instead catalyzes C-hydroxylation of the same nitro enolate substrate. These enzymes were reconstituted with Mn(II) and V(IV) horizontal lineO as mimics of the resting (Fe(II)) and reactive (Fe(IV) horizontal lineO) intermediate states, respectively. Corresponding crystal structures of the cyclopropanase bound with a substrate imply H atom transfer via an offline pi-pathway. In contrast, analogous structural analysis of the hydroxylase implies H atom abstraction likely proceeds through a sigma-pathway. Preparation of isotopically labeled substrates and stopped-flow kinetic analyses indicate that while the pro-S hydrogen of C4 is abstracted in both enzymes, the Fe(IV) horizontal lineO intermediate reacts ca. 17-fold faster in the active site of the hydroxylase, consistent with the mechanistic assignments. These results also support a correlation between the mechanism of H atom transfer and the subsequent fate of the substrate radical once generated. A subtle difference in substrate positioning not only affects the H atom abstraction pathway but also allows the nitro enolate moiety to intercept the resulting substrate radical in the active site of the cyclopropase, thereby facilitating intramolecular C-C bond formation in a stereoselective manner. Comparison of a Nonheme Iron Cyclopropanase with a Homologous Hydroxylase Reveals Mechanistic Features Associated with Distinct Reaction Outcomes.,Zheng YC, Li X, Cha L, Paris JC, Michael C, Ushimaru R, Ogasawara Y, Abe I, Guo Y, Chang WC J Am Chem Soc. 2025 Feb 3. doi: 10.1021/jacs.4c17741. PMID:39901767 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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