Characterization of HIV-1 protease autoprocessing trans-cleavage mechanism
| dc.contributor.author | Machihara, Satoshi, author | |
| dc.contributor.author | Chen, Chaoping, advisor | |
| dc.contributor.author | Ross, Eric, committee member | |
| dc.contributor.author | Rovnak, Joel, committee member | |
| dc.date.accessioned | 2007-01-03T04:21:07Z | |
| dc.date.available | 2016-06-30T05:57:00Z | |
| dc.date.issued | 2014 | |
| dc.description.abstract | HIV protease is an aspartic acid enzyme responsible for the cleavage reactions essential in the maturation (infectivity) of the viral particle. Protease inhibitors (non-cleavable substrate analogs) have been potent tools in combating HIV infection as well as its result - AIDS. However, the emergence of drug-resistant viruses in patients treated with these inhibitors is an ongoing concern. Thus there is a growing need to find additional therapeutic targets and treatments to supplement the currently available protease inhibitors. A promising new target for drug development is protease autoprocessing which is a virus-specific process responsible for the release of the mature protease from its precursor (Gag-Pol). Unfortunately, structural and mechanistic information pertaining to autoprocessing are yet insufficient. According to the mature protease structure, it is speculated that precursor dimerization is essential for autoprocessing to occur. We have developed a model system to specifically examine the trans-cleavage mechanism mediated by engineered fusion precursors (differentially labeled substrate and enzyme, respectively). Using this system, we demonstrate that trans-cleavage happens between fusion precursors both in the presence and absence of a dimer inducing fusion tag (DIFT). Trans-cleavage was also observed when monomeric fusion tags were attached to the fusion precursor. These results hint that autoprocessing mediated by the fusion precursor is independent of dimer-inducing tag in our model system. | |
| dc.format.medium | born digital | |
| dc.format.medium | masters theses | |
| dc.identifier | Machihara_colostate_0053N_12361.pdf | |
| dc.identifier.uri | http://hdl.handle.net/10217/82908 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.title | Characterization of HIV-1 protease autoprocessing trans-cleavage mechanism | |
| dc.type | Text | |
| dcterms.embargo.expires | 2016-06-30 | |
| dcterms.embargo.terms | 2016-06-30 | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Biochemistry and Molecular Biology | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.S.) |
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