5n82

Crystal structure of an engineered TycA variant in complex with an beta-Phe-AMP analog

spinqualitylabelsall models 5n82, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5n82 is a 1 chain structure with sequence from Brevibacillus parabrevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.708Å Ligands: 8PZ, BTB, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TYCA_BREPA In the first step of peptide synthesis this enzyme activates phenylalanine and racemizes it to the D-isomer. Publication Abstract from PubMed Biosynthetic modification of nonribosomal peptide backbones represents a potentially powerful strategy to modulate the structure and properties of an important class of therapeutics. Using a high-throughput assay for catalytic activity, we show here that an L-Phe-specific module of an archetypal nonribosomal peptide synthetase can be reprogrammed to accept and process the backbone-modified amino acid (S)-beta-Phe with near-native specificity and efficiency. A co-crystal structure with a non-hydrolysable aminoacyl-AMP analogue reveals the origins of the 40,000-fold alpha/beta-specificity switch, illuminating subtle but precise remodelling of the active site. When the engineered catalyst was paired with downstream module(s), (S)-beta-Phe-containing peptides were produced at preparative scale in vitro (~1 mmol) and high titres in vivo (~100 mg l(-1)), highlighting the potential of biosynthetic pathway engineering for the construction of novel nonribosomal beta-frameworks. Nonribosomal biosynthesis of backbone-modified peptides.,Niquille DL, Hansen DA, Mori T, Fercher D, Kries H, Hilvert D Nat Chem. 2018 Mar;10(3):282-287. doi: 10.1038/nchem.2891. Epub 2017 Nov 20. PMID:29461527 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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