2v22

REPLACE: A STRATEGY FOR ITERATIVE DESIGN OF CYCLIN BINDING GROOVE INHIBITORSREPLACE: A STRATEGY FOR ITERATIVE DESIGN OF CYCLIN BINDING GROOVE INHIBITORS

Structural highlights 2v22 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 1aq1, 1b38, 1b39, 1buh, 1ckp, 1di8, 1dm2, 1e1v, 1e1x, 1e9h, 1f5q, 1fin, 1fq1, 1fvt, 1fvv, 1g5s, 1gih, 1gii, 1gij, 1gy3, 1gz8, 1h00, 1h01, 1h07, 1h08, 1h0v, 1h0w, 1h1p, 1h1q, 1h1r, 1h1s, 1h24, 1h25, 1h26, 1h27, 1h28, 1hck, 1hcl, 1jst, 1jsu, 1jsv, 1jvp, 1ke5, 1ke6, 1ke7, 1ke8, 1ke9, 1ogu, 1oi9, 1oiq, 1oir, 1oit, 1oiu, 1oiy, 1okv, 1okw, 1ol1, 1ol2, 1p2a, 1p5e, 1pf8, 1pkd, 1pw2, 1pxi, 1pxj, 1pxk, 1pxl, 1pxm, 1pxn, 1pxo, 1pxp, 1pye, 1qmz, 1r78, 1urc, 1urw, 1v1k, 1vyw, 1vyz, 1w0x, 1w8c, 1w98, 1wcc, 1y8y, 1y91, 1ykr, 2a0c, 2a4l, 2b52, 2b53, 2b54, 2b55, 2bhe, 2bhh, 2bkz, 2bpm, 2btr, 2bts, 2c4g, 2c5n, 2c5o, 2c5p, 2c5t, 2c5v, 2c5x, 2c5y, 2c68, 2c69, 2c6i, 2c6k, 2c6l, 2c6m, 2c6o, 2c6t, 2cch, 2cci, 2cjm, 2clx, 2exm, 2iw6, 2iw8, 2iw9, 2j9m, 2jgz, 2uue, 2uzb, 2uzd, 2uze, 2uzl, 2uzn, 2uzo, 2v0d Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed We describe a drug-design strategy termed REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) in which nonpeptidic surrogates for specific determinants of known peptide ligands are identified in silico by using a core peptide-bound protein structure as a design anchor. In the REPLACE application example, we present the effective replacement of two critical binding motifs in a lead protein-protein interaction inhibitor pentapeptide with more druglike phenyltriazole and diphenyl ether groups. These were identified through docking of fragment libraries into the volume of the cyclin-binding groove of CDK2/cyclin A vacated through truncation of the inhibitor peptide-binding determinants. Proof of concept for this strategy was obtained through the generation of potent peptide-small-molecule hybrids and by the confirmation of inhibitor-binding modes in X-ray crystal structures. This method therefore allows nonpeptide fragments to be identified without the requirement for a high-sensitivity binding assay and should be generally applicable in replacing amino acids as individual residues or groups in peptide inhibitors to generate pharmaceutically acceptable lead molecules. REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors.,Andrews MJ, Kontopidis G, McInnes C, Plater A, Innes L, Cowan A, Jewsbury P, Fischer PM Chembiochem. 2006 Dec;7(12):1909-15. PMID:17051658 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein kinase 2 Cyclin

spinqualitylabelsall models 2v22, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image