8e1e | pdb_00008e1e

Scaffolding protein functional sites using deep learning

spinqualitylabelsall models 8e1e, resolution 4.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8e1e is a 3 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 4.27Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A challenge for design of protein-small-molecule recognition is that incorporation of cavities with size, shape, and composition suitable for specific recognition can considerably destabilize protein monomers. This challenge can be overcome through binding pockets formed at homo-oligomeric interfaces between folded monomers. Interfaces surrounding the central homo-oligomer symmetry axes necessarily have the same symmetry and so may not be well suited to binding asymmetric molecules. To enable general recognition of arbitrary asymmetric substrates and small molecules, we developed an approach to designing asymmetric interfaces at off-axis sites on homo-oligomers, analogous to those found in native homo-oligomeric proteins such as glutamine synthetase. We symmetrically dock curved helical repeat proteins such that they form pockets at the asymmetric interface of the oligomer with sizes ranging from several angstroms, appropriate for binding a single ion, to up to more than 20 A across. Of the 133 proteins tested, 84 had soluble expression in E. coli, 47 had correct oligomeric states in solution, 35 had small-angle X-ray scattering (SAXS) data largely consistent with design models, and 8 had negative-stain electron microscopy (nsEM) 2D class averages showing the structures coming together as designed. Both an X-ray crystal structure and a cryogenic electron microscopy (cryoEM) structure are close to the computational design models. The nature of these proteins as homo-oligomers allows them to be readily built into higher-order structures such as nanocages, and the asymmetric pockets of these structures open rich possibilities for small-molecule binder design free from the constraints associated with monomer destabilization. Design of Diverse Asymmetric Pockets in De Novo Homo-oligomeric Proteins.,Gerben SR, Borst AJ, Hicks DR, Moczygemba I, Feldman D, Coventry B, Yang W, Bera AK, Miranda M, Kang A, Nguyen H, Baker D Biochemistry. 2023 Jan 17;62(2):358-368. doi: 10.1021/acs.biochem.2c00497. Epub , 2023 Jan 10. PMID:36627259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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