6ve0

Crystal structure of reduced SfmD by soaking with sodium hydrosulfite

spinqualitylabelsall models 6ve0, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ve0 is a 1 chain structure with sequence from Streptomyces lavendulae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.15Å Ligands: HEC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SFMD_STRLA Heme-containing peroxygenase that mediates the hydroxylation of 3-methyl-L-tyrosine (3-Me-Tyr) into 3-hydroxy-5-methyl-L-tyrosine (3-OH-5-Me-Tyr) in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family. Involved in biosynthesis of 3-hydroxy-5-methyl-O-methyltyrosine (3-OH-5-Me-OMe-Tyr), a core structure of saframycin A. Publication Abstract from PubMed SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78 A resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor attached to the protein with an unusual Hx n HxxxC motif (n approximately 38). This heme cofactor is unique in two respects. It contains a single thioether bond in a cysteine-vinyl link with Cys317, and the ferric heme has two axial protein ligands, i.e., His274 and His313. We demonstrated that SfmD heme is catalytically active and can utilize dioxygen and ascorbate for a single-oxygen insertion into 3-methyl-l-tyrosine. Catalytic assays using ascorbate derivatives revealed the functional groups of ascorbate essential to its function as a cosubstrate. Abolishing the thioether linkage through mutation of Cys317 resulted in catalytically inactive SfmD variants. EPR and optical data revealed that the heme center undergoes a substantial conformational change with one axial histidine ligand dissociating from the iron ion in response to substrate 3-methyl-l-tyrosine binding or chemical reduction by a reducing agent, such as the cosubstrate ascorbate. The labile axial ligand was identified as His274 through redox-linked structural determinations. Together, identifying an unusual heme cofactor with a previously unknown heme-binding motif for a monooxygenase activity and the structural similarity of SfmD to the members of the heme-based tryptophan dioxygenase superfamily will broaden understanding of heme chemistry. A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by a de novo crystal structural and spectroscopic study.,Shin I, Davis I, Nieves-Merced K, Wang Y, McHardy S, Liu A Chem Sci. 2021 Jan 22;12(11):3984-3998. doi: 10.1039/d0sc06369j. PMID:34163669 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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