114 research outputs found
soaPDB: a web application for searching the Protein Data Bank, organizing results, and receiving automatic email alerts
soaPDB is a web application that allows generation and organization of saved PDB searches, and offers automatic email alerts. This tool is used from a web interface to store PDB searches and results in a backend relational database. Written using the Ruby on Rails open-source web framework, soaPDB is easy to deploy, maintain and customize. soaPDB is freely available upon request for local installation and is also available at http://soapdb.dyndns.org:3000
Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates
Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (trans,trans)-farnesyl diphosphate (FPP) (1a) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (cis,trans)-FPP (1b) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (cis,trans)-FPP (1b) to exclusively (≥99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-trans FPP (1a) and (cis,trans)-FPP (1b) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed
StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase
Simple but Highly Effective Three-Dimensional Chemical-Feature-Based Pharmacophore Model for Diketo Acid Derivatives as Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibitors
Discovery of hit molecules targeting allosteric site of hepatitis C virus NS5B polymerase
Influence of Amiloride Derivatives on Alpha-i Adrenergic Receptor-Induced Contractions of the Rabbit Aorta
XGen: Real-Space Fitting of Complex Ligand Conformational Ensembles to X-ray Electron Density Maps
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