1urc

Cyclin A binding groove inhibitor Ace-Arg-Lys-Leu-Phe-GlyCyclin A binding groove inhibitor Ace-Arg-Lys-Leu-Phe-Gly

Structural highlights 1urc is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: Related: 1aq1, 1b38, 1b39, 1buh, 1ckp, 1di8, 1dm2, 1e1v, 1e1x, 1e9h, 1f5q, 1fin, 1fq1, 1fvt, 1fvv, 1g5s, 1gih, 1gii, 1gij, 1gy3, 1gz8, 1h00, 1h01, 1h06, 1h07, 1h08, 1h0u, 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, 1oku, 1okv, 1okw, 1ol1, 1ol2, 1p2a, 1p5e, 1pkd, 1qmz 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 Inhibition of cyclin A- and cyclin E-associated cyclin-dependent kinase-2 (CDK2) activities is an effective way of selective induction of apoptotic cell death via the E2F pathway in tumour cells. The cyclin groove recognition motif (CRM) in the natural CDK-inhibitory (CDKI) tumour suppressor protein p27KIP1 was used as the basis for the design and synthesis of a series of cyclic peptides whose biological activity and structural characterisation by NMR and X-ray crystallography is reported. Whereas linear p27KIP1 sequence peptides were comparatively ineffective, introduction of side chain-to-tail constraints was found to be productive. An optimal macrocyclic ring size for the conformational constraint was determined, mimicking the intramolecular H-bonding system of p27. Molecular dynamics calculations of various macrocycles suggested a close correlation between ring flexibility and biological activity. Truncated inhibitor peptide analogues also confirmed the hypothesis that introduction of a cyclic conformational constraint is favourable in terms of affinity and potency. The structural basis for the potency increase in cyclic versus linear peptides was demonstrated through the determination and interpretation of X-ray crystal structures of complexes between CDK2/cylin A (CDK2A) and a constrained pentapeptide. Design, synthesis, biological activity and structural analysis of cyclic peptide inhibitors targeting the substrate recruitment site of cyclin-dependent kinase complexes.,Andrews MJ, McInnes C, Kontopidis G, Innes L, Cowan A, Plater A, Fischer PM Org Biomol Chem. 2004 Oct 7;2(19):2735-41. Epub 2004 Sep 9. PMID:15455144 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein kinase 2 Cyclin

spinqualitylabelsall models 1urc, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image