9ca3 | pdb_00009ca3

Crystal structure of MarE C280S in complex with cyanide bound heme and its native substrate, beta-methyl-L-tryptophan

spinqualitylabelsall models 9ca3, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ca3 is a 4 chain structure with sequence from Streptomyces sp. B9173. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.89Å Ligands: 78U, CYN, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function X2D878_9ACTN Publication Abstract from PubMed MarE, a heme-dependent enzyme, catalyzes a unique 2-oxindole-forming monooxygenation reaction from tryptophan metabolites. To elucidate its enzyme-substrate interaction mode, we present the first X-ray crystal structures of MarE in complex with its prime substrate, (2S,3S)-beta-methyl-l-tryptophan and cyanide at 1.89 A resolution as well as a truncated yet catalytically active version in complex with the substrate at 2.45 A resolution. These structures establish MarE as a member of the heme-dependent aromatic oxygenase (HDAO) superfamily and reveal its evolutionary link to indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). While MarE adopts a global structure resembling the homotetrameric TDO, it features a simplified alpha6 helix compared to TDO's more elaborate alphaE and alphaH helices with additional alphaF and alphaG regions. Despite differing oxygen activation outcomes, MarE shares a substrate binding mode similar to IDO and TDO, with the indole nitrogen of its substrate oriented toward the heme iron in the ternary cyano complex, interacting with His55. The substrate's carboxylate group engages Arg118, with mutational studies confirming the roles of these residues in substrate binding. However, the second-sphere interactions with the substrate's alpha-amino nitrogen differ between MarE and TDO, and the substrate's orientation in the binary complex remains ambiguous due to two possible conformations. Notably, TDO features an extensive hydrogen-bonding network around the heme propionate below the heme plane, which is absent in MarE, suggesting mechanistic differences. These structural insights lay a foundation for further mechanistic studies, particularly for understanding how heme-dependent enzymes oxygenate tryptophan-derived metabolites. Structural insights into 2-oxindole-forming monooxygenase MarE: Divergent architecture and substrate positioning versus tryptophan dioxygenases.,Shin I, Nguyen RC, Montoya SR, Liu A J Biol Chem. 2025 Jan 27;301(3):108241. doi: 10.1016/j.jbc.2025.108241. PMID:39880093 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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