Sandbox Reserved 430
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==Introduction== | ==Introduction== | ||
| - | The goal of pharmaceuticals is to prevent or cure disease through drug therapy by specifically targeting cells, proteins, enzymes, genes, etc. It is often crucial to understand the structure, function, and relevant mechanisms involved with the target when designing an effective drug candidate. Furthermore, being able to know the effects on structure after drug-binding can provide insight into the functionality of a specific target. Because of this fact, it is common practice for research labs to develop protein crystals and use methods like x-ray diffraction, electron density mapping, and nuclear magnetic resonance spectroscopy to model the full structure. In this case, P2Y12, a member of P2Y receptor, was modeled when binded to | + | The goal of pharmaceuticals is to prevent or cure disease through drug therapy by specifically targeting cells, proteins, enzymes, genes, etc. It is often crucial to understand the structure, function, and relevant mechanisms involved with the target when designing an effective drug candidate. Furthermore, being able to know the effects on structure after drug-binding can provide insight into the functionality of a specific target. Because of this fact, it is common practice for research labs to develop protein crystals and use methods like x-ray diffraction, electron density mapping, and nuclear magnetic resonance spectroscopy to model the full structure. In this case, P2Y12, a member of P2Y receptor, was modeled when binded to AZD1283, an engineered receptor inhibitor.The molecular scene shows the chemical<scene name='48/483887/Here_is/1'> model</scene> of P2Y12 with the anionic side chains in red and charged nucleic acids and ligands in grey for contrast. |
| - | Image analysis of P2Y12 crystals is used to model protein structure in complex with AstraZeneca’s novel | + | Image analysis of P2Y12 crystals is used to model protein structure in complex with AstraZeneca’s novel AZD1283: Ethyl 6-(4(-((benzylsulphonyl)carbamoyl)piperidin-1yl)-5-cyano-2-methylnicotinate. AZD1283 functions to block the P2Y12 receptor as a means to treat thrombosis. AZD1283-binding leads to unique protein structure, unfound in other P2Y receptors. Helix V of seven transmembrane helices is found to be <scene name='48/483887/Helix_vii/1'>elongated and straightened</scene>. This change along with the discovery of a potential second active within P2Y12 has implications on how P2Y12 uses it’s seven transmembrane helical bundle interact with ADP in the bloodstream. |
As a member of a large class of G-protein-coupled receptors, P2Y12 is often an initial role player in signal transduction and cellular response due to external environmental factors. In the case of P2Y12, the receptor responds to ADP concentrations in the extracellular matrix and on a larger scale the blood stream. There is importance is understanding how P2Y12's structure receives ADP as an activator. In turn, knowledge of how P2Y12 is affected when properly inhibited can lead to improved drug design in terms of bioavailability, binding affinity, and effectiveness of inhibition. Ultimately, pharmaceuticals will be better able to prevent and treat cardiovascular diseases and medical conditions (thrombosis, hypercoagulable states) and more immediate dangers (stroke, embolism, and heart attacks). | As a member of a large class of G-protein-coupled receptors, P2Y12 is often an initial role player in signal transduction and cellular response due to external environmental factors. In the case of P2Y12, the receptor responds to ADP concentrations in the extracellular matrix and on a larger scale the blood stream. There is importance is understanding how P2Y12's structure receives ADP as an activator. In turn, knowledge of how P2Y12 is affected when properly inhibited can lead to improved drug design in terms of bioavailability, binding affinity, and effectiveness of inhibition. Ultimately, pharmaceuticals will be better able to prevent and treat cardiovascular diseases and medical conditions (thrombosis, hypercoagulable states) and more immediate dangers (stroke, embolism, and heart attacks). | ||
Revision as of 00:55, 11 April 2016
| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
P2Y12 Receptor in Complex with AZD1283 (4ntj)[1]
by [Cora Ricker, Lauren Timmins, Aidan Finnerty, Adam Murphy, Duy Nguyen]
Student Projects for UMass Chemistry 423 Spring 2016
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