4cpi

streptavidin A86D mutant with love-hate ligand 4

spinqualitylabelsall models 4cpi, resolution 1.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cpi is a 4 chain structure with sequence from Streptomyces avidinii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.54Å Ligands: CA, LH4, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SAV_STRAV The biological function of streptavidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of streptavidin). Publication Abstract from PubMed The pathway of ligand dissociation and how binding sites respond to force are not well understood for any macromolecule. Force effects on biological receptors have been studied through simulation or force spectroscopy, but not by high resolution structural experiments. To investigate this challenge, we took advantage of the extreme stability of the streptavidin-biotin interaction, a paradigm for understanding non-covalent binding as well as a ubiquitous research tool. We synthesized a series of biotin-conjugates having an unchanged strong-binding biotin moiety, along with pincer-like arms designed to clash with the protein surface: 'Love-Hate ligands'. The Love-Hate ligands contained various 2,6-di-ortho aryl groups, installed using Suzuki coupling as the last synthetic step, making the steric repulsion highly modular. We determined binding affinity, as well as solving 1.1-1.6A resolution crystal structures of streptavidin bound to Love-Hate ligands. Striking distortion of streptavidin's binding contacts was found for these complexes. Hydrogen bonds to biotin's ureido and thiophene rings were preserved for all the ligands, but biotin's valeryl tail was distorted from the classic conformation. Streptavidin's L3/4 loop, normally forming multiple energetically-important hydrogen bonds to biotin, was forced away by clashes with Love-Hate ligands, but Ser45 from L3/4 could adapt to hydrogen-bond to a different part of the ligand. This approach of preparing conflicted ligands represents a direct way to visualize strained biological interactions and test protein plasticity. Love-Hate ligands for high resolution analysis of strain in ultra-stable protein/small molecule interaction.,Fairhead M, Shen D, Chan LK, Lowe ED, Donohoe TJ, Howarth M Bioorg Med Chem. 2014 Jul 24. pii: S0968-0896(14)00545-8. doi:, 10.1016/j.bmc.2014.07.029. PMID:25128469 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Avidin 3D structures

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