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Crystallographic Study Of Hiv Protease Drug Resistant Variants And Green Fluorescent Protein Based Calcium Sensor Catcher, Ying Zhang
Chemistry Dissertations
HIV-1 protease is an important enzyme for the maturation of infectious virions and has been an effective drug target for HIV/AIDS. Protease inhibitors were successfully designed based on the structural data for AIDS therapy. Nonetheless, the drug resistant PR variants are selected rapidly during therapy. Mutation L76V is associated with drug resistance and shows opposite effects on different protease inhibitors. Kinetics and stability of PRL76V were studied and high-resolution crystal structures of PRL76V with inhibitors were solved to identify structural changes. HIV-1 PRP51 variant is a multiple mutant selected for resistance to darunavir in the laboratory in …
Crystallographic Analysis And Kinetic Studies Of Hiv-1 Protease And Drug-Resistant Mutants, Yunfeng Tie
Crystallographic Analysis And Kinetic Studies Of Hiv-1 Protease And Drug-Resistant Mutants, Yunfeng Tie
Chemistry Dissertations
HIV-1 protease is the most effective target for drugs to treat AIDS, however, the long-term therapeutic efficiency is restricted by the rapid development of drug resistant variants. To better understand the molecular basis of drug resistance, crystallographic and kinetic studies were applied to wild-type HIV-1 protease (PR) and drug-resistant mutants, PRV82A, and PRI84V, in complex with substrate analogues, the current drug saquinavir and the new inhibitor UIC-94017 (TMC-114). UIC-94017 was also studied with mutants PRD30N and PRI50V. The drug-resistant mutations V82A, I84V, D30N and I50V participate in substrate binding. Eighteen crystal structures were refined at resolutions of 0.97-1.60A. The high …