Grant: $55,387 - National Institutes of Health - Sep. 30, 2009
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Award Description: Ubiquitin-like modifications are similar to other macromolecular chemistry, such as transcription and DMArepair, in that they require multiple steps that are carried out by multi- protein complexes. Better understanding of how the multi-protein machinery catalyzes ubiquitin- like modifications is fundamentally important and will significantly improve our knowledge of how multi-protein complexes carry out macromolecular chemistry. The overall goal of this proposal is to investigate the enzymology of protein modifications by the small ubiquitin-like modifier (SUMO). Sumoylation, which is established as an important post-translational modification, is a good model system for enzymology studies, and has been proposed as a cancer therapeutic target, because of the increased levels of its enzymes in cancers. A mystery about the enzymology is that the binding substrates are too far apart from the catalytic sites in crystal structures to account for catalysis, and the prevailing view is that conformational changes must take place to bring them into close proximity. As shown in our Preliminary Studies section, while the available structures are stable complexes, less stable interactions that have not been characterized are critical to the enzymatic cycle. We will investigate how the weaker interactions may guide substrate translocations to catalytic active sites, and induce allosteric effects in the enzymes. We will use NMR spectroscopy in structural studies, which is especially suitable for characterizing weak protein complexes. Complementary biochemical and enzyme kinetic analysis will be used to identify the role of each interaction in the enzyme mechanism. The proposed studies will likely result in a paradigm shift regarding the enzymes catalyzing ubiquitin-like modifications, and improve our knowledge of the themes and variations of how multi-protein machineries catalyze macromolecular reactions.
Project Description: Funds will be use to purchase 'AKTA Protein Purifier Equipment' The equipment will help accelerating the pace of research of the Parent Grant - R01GM074748.
Jobs Summary: Project start date is 9/30/09. There have been no jobs created or retained. (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 30, 2009. Help expand these official descriptions using the wiki below.