4jmz

Crystal structure of Cytochrome C Peroxidase W191G-Gateless in complex with N-methyl-1H-benzimidazol-2-amine

spinqualitylabelsall models 4jmz, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jmz is a 1 chain structure with sequence from Saccharomyces cerevisiae RM11-1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.82Å Ligands: 1M2, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B3LRE1_YEAS1 Publication Abstract from PubMed A key challenge in structure-based discovery is accounting for modulation of protein-ligand interactions by ordered and bulk solvent. To investigate this, we compared ligand binding to a buried cavity in Cytochrome c Peroxidase (CcP), where affinity is dominated by a single ionic interaction, versus a cavity variant partly opened to solvent by loop deletion. This opening had unexpected effects on ligand orientation, affinity, and ordered water structure. Some ligands lost over ten-fold in affinity and reoriented in the cavity, while others retained their geometries, formed new interactions with water networks, and improved affinity. To test our ability to discover new ligands against this opened site prospectively, a 534,000 fragment library was docked against the open cavity using two models of ligand solvation. Using an older solvation model that prioritized many neutral molecules, three such uncharged docking hits were tested, none of which was observed to bind; these molecules were not highly ranked by the new, context-dependent solvation score. Using this new method, another 15 highly-ranked molecules were tested for binding. In contrast to the previous result, 14 of these bound detectably, with affinities ranging from 8 microM to 2 mM. In crystal structures, four of these new ligands superposed well with the docking predictions but two did not, reflecting unanticipated interactions with newly ordered waters molecules. Comparing recognition between this open cavity and its buried analog begins to isolate the roles of ordered solvent in a system that lends itself readily to prospective testing and that may be broadly useful to the community. Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities.,Barelier S, Boyce SE, Fish I, Fischer M, Goodin DB, Shoichet BK PLoS One. 2013 Jul 18;8(7):e69153. doi: 10.1371/journal.pone.0069153. Print 2013. PMID:23874896 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome c peroxidase 3D structures

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