8itg | pdb_00008itg

Crystal structure of lasso peptide epimerase MslH in complexed with precursor peptide variant MslAW21G

spinqualitylabelsall models 8itg, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8itg is a 2 chain structure with sequence from Streptomyces griseorubiginosus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: CA, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The lasso peptide MS-271 is a ribosomally synthesized and post-translationally modified peptide (RiPP) consisting of 21 amino acids with D-tryptophan at the C-terminus, and is derived from the precursor peptide MslA. MslH, encoded in the MS-271 biosynthetic gene cluster (msl), catalyzes the epimerization at the Calpha center of the MslA C-terminal Trp21, leading to epi-MslA. The detailed catalytic process, including the catalytic site and cofactors, has remained enigmatic. Herein, based on X-ray crystallographic studies in association with MslA core peptide analogues, we show that MslH is a metallo-dependent peptide epimerase with a calcineurin-like fold. The crystal structure analysis, followed by site-directed mutagenesis, docking simulation, and ICP-MS studies demonstrate that MslH employs acid/base chemistry to facilitate the reversible epimerization of the C-terminal Trp21 of MslA, by utilizing two pairs of His/Asp catalytic residues that are electrostatically tethered to a six-coordination motif with a Ca(II) ion via water molecules. Structure of lasso peptide epimerase MslH reveals metal-dependent acid/base catalytic mechanism.,Nakashima Y, Kawakami A, Ogasawara Y, Maeki M, Tokeshi M, Dairi T, Morita H Nat Commun. 2023 Aug 8;14(1):4752. doi: 10.1038/s41467-023-40232-x. PMID:37550286 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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