2q5a | pdb_00002q5a

human Pin1 bound to L-PEPTIDE

spinqualitylabelsall models 2q5a, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2q5a is a 2 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2iti. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 16P NonStd Res: ACE, NAL, NH2, TPO, YCP Related: 2itk, 1pin Gene: PIN1 (Homo sapiens) Activity: Peptidylprolyl isomerase, with EC number 5.2.1.8 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 Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I beta-turn conformation for Pin1 prolyl peptide isomerase domain-peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors. Structural basis for high-affinity peptide inhibition of human Pin1.,Zhang Y, Daum S, Wildemann D, Zhou XZ, Verdecia MA, Bowman ME, Lucke C, Hunter T, Lu KP, Fischer G, Noel JP ACS Chem Biol. 2007 May 22;2(5):320-8. PMID:17518432 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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