3kai

Structure-guided design of alpha-amino acid-derived Pin1 inhibitorsStructure-guided design of alpha-amino acid-derived Pin1 inhibitors

Structural highlights 3kai is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 3kab, 3kac, 3kad, 3kaf, 3kag, 3kah, 3kce 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 The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC(50) <100nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells. Structure-guided design of alpha-amino acid-derived Pin1 inhibitors.,Potter AJ, Ray S, Gueritz L, Nunns CL, Bryant CJ, Scrace SF, Matassova N, Baker L, Dokurno P, Robinson DA, Surgenor AE, Davis B, Murray JB, Richardson CM, Moore JD Bioorg Med Chem Lett. 2010 Jan 15;20(2):586-90. Epub 2009 Nov 22. PMID:19969456 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 3kai, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image