4rjf

Crystal structure of the human sliding clamp at 2.0 angstrom resolution

spinqualitylabelsall models 4rjf, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rjf 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. Method: X-ray diffraction, Resolution 2.0072Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CDN1A_HUMAN May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Publication Abstract from PubMed Proliferating cell nuclear antigen (PCNA, processivity factor, sliding clamp) is a ring-shaped protein that tethers proteins to DNA in processes, including DNA replication, DNA repair, and cell-cycle control. Often used as a marker for cell proliferation, PCNA is overexpressed in cancer cells, making it an appealing pharmaceutical target. PCNA interacts with proteins through a PCNA interacting protein (PIP)-box, an eight-amino acid consensus sequence; different binding partners display a wide range of affinities based on function. Of all biological PIP-boxes, p21 has the highest known affinity for PCNA, allowing for inhibition of DNA replication and cell growth under cellular stress. As p21 is one of the few PIP-box sequences to contain a tyrosine rather than a phenylalanine in the eighth conserved position, we probed the significance of the hydroxyl group at this position using a mutational approach. Here we present the cocrystal structure of PCNA bound to a mutant p21 PIP-box peptide, p21Tyr151Phe, with associated isothermal titration calorimetry data. The p21Tyr151Phe peptide showed a 3-fold difference in affinity, as well as differences in entropy and enthalpy of binding. These differences can be attributed to a loss of hydrogen bonding capacity, as well as structural plasticity in the PCNA interdomain connector loop and the hydrophobic cavity of PCNA to which p21 binds. Thus, the hydroxyl group of Tyr151 in p21 acts as a tethering point for ideal packing and surface recognition of the peptide interface, increasing the binding affinity of p21 for PCNA. p21 Exploits Residue Tyr151 as a Tether for High-Affinity PCNA Binding.,Kroker AJ, Bruning JB Biochemistry. 2015 Jun 9;54(22):3483-93. doi: 10.1021/acs.biochem.5b00241. Epub, 2015 May 27. PMID:25972089 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proliferating cell nuclear antigen 3D structures

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