2x1n

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 2x1n is a 5 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2wha. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NonStd Res: , , Related: 1h08, 1pye, 2vth, 2b53, 1v1k, 1ke7, 1okv, 1h25, 1pxk, 2wih, 2bhh, 2vta, 2uue, 1gz8, 1e1v, 1ol2, 1h27, 1jsv, 2wha, 2b52, 1ke5, 1fin, 2c5o, 2c68, 2vtt, 1p2a, 2vtq, 2c4g, 1h1q, 1w0x, 2w05, 1pxo, 1ke9, 2a0c, 1hck, 1jsu, 1pxn, 2uze, 2v0d, 2vtm, 1oiq, 1h1r, 2iw8, 1hcl, 1pw2, 1gih, 2whb, 2vtn, 2w06, 1jst, 1oiu, 1b38, 1pxm, 1fq1, 1vyw, 1h1p, 2wma, 2c69, 1urc, 1pxi, 2c6i, 2wxv, 1ykr, 2w17, 2uzd, 2c6k, 2c5y, 1wcc, 2j9m, 1vyz, 2vti, 1jvp, 1w98, 2wip, 1pkd, 1p5e, 2vts, 2c5p, 2uzn, 2b54, 1ke6, 1pxj, 2uzl, 2cci, 2bkz, 2g9x, 1y91, 2iw6, 1gij, 1r78, 1h0v, 2iw9, 1w8c, 1buh, 2bpm, 2bts, 1fvv, 1okw, 2vtp, 2a4l, 2c6t, 1fvt, 1qmz, 2w1h, 2vu3, 2b55, 1ogu, 1pf8, 1h1s, 2c5v, 2jgz, 2bhe, 1urw, 1oiy, 2c6l, 1f5q, 2c6o, 2vtl, 1ol1, 1h01, 2wfy, 2uzb, 1oir, 1oi9, 2vtj, 2cjm, 2c5x, 2wev, 2c5n, 2c6m, 1oit, 2v22, 1gy3, 1di8, 1gii, 2vv9, 2wpa, 1e9h, 2wmb, 2vto, 1dm2, 1h24, 2uzo, 2exm, 1h00, 2clx, 1pxp, 2cch, 1b39, 2btr, 1aq1, 1h0w, 1g5s, 1ckp, 1ke8, 1h28, 1pxl, 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 Following the recent discovery and development of 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin dependent kinase (CDK) inhibitors, a program was initiated to evaluate related ring-constrained analogues, specifically, 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines for inhibition of CDKs. Here we report the rational design, synthesis, structure-activity relationships (SARs), and cellular mode-of-action profile of these second generation CDK inhibitors. Many of the analogues from this chemical series inhibit CDKs with very low nanomolar K(i) values. The most potent compound reported in this study inhibits CDK2 with an IC(50) of 0.7 nM ([ATP] = 100 microM). Furthermore, an X-ray crystal structure of 2-methyl-N-(3-(nitro)phenyl)-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine (11g), a representative from the chemical series in complex with cyclin A-CDK2, is reported, confirming the design rationale and expected binding mode within the CDK2 ATP binding pocket. Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors.,McIntyre NA, McInnes C, Griffiths G, Barnett AL, Kontopidis G, Slawin AM, Jackson W, Thomas M, Zheleva DI, Wang S, Blake DG, Westwood NJ, Fischer PM J Med Chem. 2010 Mar 11;53(5):2136-45. PMID:20146435 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein kinase 2 Cyclin

spinqualitylabelsall models 2x1n, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image