3upe | pdb_00003upe

Bovine trypsin variant X(triplePhe227) in complex with small molecule inhibitor

spinqualitylabelsall models 3upe, resolution 1.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3upe is a 1 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0CA, CA, GOL, SO4 Related: 1v2k, 3unq, 3uns, 3unp, 3uqo, 3uqv, 3uqz Activity: Trypsin, with EC number 3.4.21.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Abstract A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein-ligand interactions and emphasize the difficulties in predicting affinity from structure. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues.,Tziridis A, Rauh D, Neumann P, Kolenko P, Menzel A, Brauer U, Ursel C, Steinmetzer P, Sturzebecher J, Schweinitz A, Steinmetzer T, Stubbs MT Biol Chem. 2014 Jul 1;395(7-8):891-903. doi: 10.1515/hsz-2014-0158. PMID:25003390 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Trypsin

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