2wev

TRUNCATION AND OPTIMISATION OF PEPTIDE INHIBITORS OF CDK2, CYCLIN A THROUGH STRUCTURE GUIDED DESIGNTRUNCATION AND OPTIMISATION OF PEPTIDE INHIBITORS OF CDK2, CYCLIN A THROUGH STRUCTURE GUIDED DESIGN

Structural highlights 2wev is a 6 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2c5p. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NonStd Res: , , , Related: 1h08, 1pye, 2vth, 1v1k, 2b53, 1h25, 1okv, 1ke7, 1pxk, 2bhh, 2vta, 2uue, 1gz8, 1e1v, 1ol2, 1h27, 1jsv, 2b52, 1ke5, 1fin, 2c5o, 2c68, 1p2a, 2vtt, 2vtq, 2c4g, 1h1q, 1w0x, 2w05, 1pxo, 1ke9, 1hck, 2a0c, 1jsu, 1pxn, 2uze, 2vtm, 2v0d, 1oiq, 1h1r, 2iw8, 1gih, 1hcl, 1pw2, 2w06, 2vtn, 1jst, 1oiu, 1pxm, 1b38, 1fq1, 1vyw, 1h1p, 2c69, 1urc, 1pxi, 2c6i, 1ykr, 2w17, 2uzd, 2c6k, 2c5y, 1wcc, 2j9m, 1vyz, 2vti, 1jvp, 1w98, 1pkd, 1p5e, 2vts, 2uzn, 2b54, 1ke6, 1pxj, 2uzl, 2cci, 2bkz, 2g9x, 1y91, 2iw6, 1gij, 1r78, 1h0v, 2iw9, 1w8c, 1buh, 2bpm, 2bts, 1fvv, 1okw, 2a4l, 2vtp, 2c6t, 1fvt, 1qmz, 2w1h, 2vu3, 2b55, 1ogu, 1pf8, 1h1s, 2c5v, 2jgz, 2bhe, 1urw, 1oiy, 2c6l, 1f5q, 2c6o, 2vtl, 1ol1, 1h01, 2uzb, 1oir, 1oi9, 2vtj, 2cjm, 2c5n, 2c5x, 2c6m, 1oit, 2v22, 1gy3, 1gii, 2vv9, 1di8, 1e9h, 1dm2, 2vto, 2uzo, 1h24, 2exm, 1h00, 2clx, 1pxp, 2cch, 1b39, 2btr, 1aq1, 1h0w, 1g5s, 1ckp, 1pxl, 1ke8, 1h28, 2vtr, 1h26, 1e1x, 1h07, 1y8y 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 The cyclin-dependent kinase 2-cyclin A complex is an important regulator of the DNA-synthesis phase of the mammalian cell cycle, which is frequently deregulated in cancer. Rather than blocking the ATP-binding site of the apparently redundant kinase subunit, targeting the binding site for macromolecular substrates and regulatory proteins of cyclin A represents a promising strategy to enforce tumour-selective apoptosis. The cyclin-binding groove can be blocked with comparatively small synthetic peptides, which indirectly leads to inhibition of kinase function, but these peptides are metabolically labile and membrane impermeable. As part of our ongoing effort to develop more druglike peptidomimetics derived from cyclin-groove-binding peptides, we report the results of our studies aimed at a detailed understanding of the structural determinants required for effective binding. Using a combination of peptide synthesis, biochemical assays and X-ray crystallography, we show that it is possible to simplify peptide structures through the replacement of dipeptide units in which one of the residues is not directly involved in binding, through the introduction of beta-amino acid residues that retain only the dipeptide residue side chain that is important for binding. This approach also allowed us to probe spatial constraints in general, as well as the importance of peptide backbone hydrogen-bonding functions. Our identification of potent beta-homoleucine-containing tetrapeptide inhibitors, as well as the finding that an optimised N-terminally acetylated tripeptide retains some cyclin A-binding affinity, suggest that the pharmacological targeting of the cyclin A binding groove may be feasible. Truncation and Optimisation of Peptide Inhibitors of Cyclin-Dependent Kinase 2-Cyclin A Through Structure-Guided Design.,Kontopidis G, Andrews MJ, McInnes C, Plater A, Innes L, Renachowski S, Cowan A, Fischer PM ChemMedChem. 2009 May 26. PMID:19472269 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein kinase 2 Cyclin

spinqualitylabelsall models 2wev, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image