4hu5

Oxime side-chain cross-links in the GCN4-p1 dimeric coiled coil: Linear precursor

spinqualitylabelsall models 4hu5, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hu5 is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 19W, ACE, ACT, GOL, NH2, NLE, UU4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GCN4_YEAST Is a transcription factor that is responsible for the activation of more than 30 genes required for amino acid or for purine biosynthesis in response to amino acid or purine starvation. Binds and recognize the DNA sequence: 5'-TGA[CG]TCA-3'. Publication Abstract from PubMed Covalent side-chain cross-links are a versatile method to control peptide folding, particularly when alpha-helical secondary structure is the target. Here, we examine the application of oxime bridges, formed by the chemoselective reaction between aminooxy and aldehyde side chains, for the stabilization of a helical peptide involved in a protein-protein complex. A series of sequence variants of the dimeric coiled coil GCN4-p1 bearing oxime bridges at solvent-exposed positions were prepared and biophysically characterized. Triggered unmasking of a side-chain aldehyde in situ and subsequent cyclization proceed rapidly and cleanly at pH 7 in the folded protein complex. Comparison of folding thermodynamics among a series of different oxime bridges show that the cross links are consistently stabilizing to the coiled coil, with the extent of stabilization sensitive to the exact size and structure of the macrocycle. X-ray crystallographic analysis of a coiled coil with the best cross link in place and a second structure of its linear precursor show how the bridge is accommodated into an alpha-helix. Preparation of a bicyclic oligomer by simultaneous formation of two linkages in situ demonstrates the potential use of triggered oxime formation to both trap and stabilize a particular peptide folded conformation in the bound state. Oxime Side-Chain Cross-Links in an alpha-Helical Coiled-Coil Protein: Structure, Thermodynamics, and Folding-Templated Synthesis of Bicyclic Species.,Haney CM, Horne WS Chemistry. 2013 Aug 19;19(34):11342-51. doi: 10.1002/chem.201300506. Epub 2013, Jul 10. PMID:23843311 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gnc4 3D Structures

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