6czi

Structure of a redesigned beta barrel, mFAP1, bound to DFHBI

spinqualitylabelsall models 6czi, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6czi is a 2 chain structure with sequence from Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 38E Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The regular arrangements of beta-strands around a central axis in beta-barrels and of alpha-helices in coiled coils contrast with the irregular tertiary structures of most globular proteins, and have fascinated structural biologists since they were first discovered. Simple parametric models have been used to design a wide range of alpha-helical coiled-coil structures, but to date there has been no success with beta-barrels. Here we show that accurate de novo design of beta-barrels requires considerable symmetry-breaking to achieve continuous hydrogen-bond connectivity and eliminate backbone strain. We then build ensembles of beta-barrel backbone models with cavity shapes that match the fluorogenic compound DFHBI, and use a hierarchical grid-based search method to simultaneously optimize the rigid-body placement of DFHBI in these cavities and the identities of the surrounding amino acids to achieve high shape and chemical complementarity. The designs have high structural accuracy and bind and fluorescently activate DFHBI in vitro and in Escherichia coli, yeast and mammalian cells. This de novo design of small-molecule binding activity, using backbones custom-built to bind the ligand, should enable the design of increasingly sophisticated ligand-binding proteins, sensors and catalysts that are not limited by the backbone geometries available in known protein structures. De novo design of a fluorescence-activating beta-barrel.,Dou J, Vorobieva AA, Sheffler W, Doyle LA, Park H, Bick MJ, Mao B, Foight GW, Lee MY, Gagnon LA, Carter L, Sankaran B, Ovchinnikov S, Marcos E, Huang PS, Vaughan JC, Stoddard BL, Baker D Nature. 2018 Sep 12. pii: 10.1038/s41586-018-0509-0. doi:, 10.1038/s41586-018-0509-0. PMID:30209393 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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