6wsj

Crystal Structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with cyclopeptide des4.3.1

spinqualitylabelsall models 6wsj, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wsj is a 2 chain structure with sequence from Danio rerio and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: DAL, DAR, DNE, DSN, EDO, K, U2M, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F8W4B7_DANRE Publication Abstract from PubMed Despite recent success in computational design of structured cyclic peptides, de novo design of cyclic peptides that bind to any protein functional site remains difficult. To address this challenge, we develop a computational "anchor extension" methodology for targeting protein interfaces by extending a peptide chain around a non-canonical amino acid residue anchor. To test our approach using a well characterized model system, we design cyclic peptides that inhibit histone deacetylases 2 and 6 (HDAC2 and HDAC6) with enhanced potency compared to the original anchor (IC(50) values of 9.1 and 4.4 nM for the best binders compared to 5.4 and 0.6 microM for the anchor, respectively). The HDAC6 inhibitor is among the most potent reported so far. These results highlight the potential for de novo design of high-affinity protein-peptide interfaces, as well as the challenges that remain. Anchor extension: a structure-guided approach to design cyclic peptides targeting enzyme active sites.,Hosseinzadeh P, Watson PR, Craven TW, Li X, Rettie S, Pardo-Avila F, Bera AK, Mulligan VK, Lu P, Ford AS, Weitzner BD, Stewart LJ, Moyer AP, Di Piazza M, Whalen JG, Greisen PJ, Christianson DW, Baker D Nat Commun. 2021 Jun 7;12(1):3384. doi: 10.1038/s41467-021-23609-8. PMID:34099674 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone deacetylase 3D structures

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