This blog supports the CH795 Special Topics in Chemistry courses taught by Dr. Gavin Williams and Dr. Alex Deiters at North Carolina State University. Please include an illustrative figure when you post a blog entry.
Friday, September 30, 2011
Crystal structure of a monomeric retroviral protease solved by protein folding game players
This article explains an unusual solution to a decade old problem. M-PMV retroviral protease has proved elusive to researchers attempting to deduce its crystal structure. Without good approximate models, determination of actual crystal structure has not been successful. Foldit, a multiplayer computer game that allows players with no biochemical foreknowledge to attempt to solve crystal structures by creating the lowest ground state energy conformations, was used by competing groups in a race to solve the crystal structure of M-PMV. Remarkably, a a group succeeded in three weeks.
Beyond directed evolution—semi-rational protein engineering and design
This review examines a computational approach to rational design. Highlighting recent engineering and design examples, while emphasizing the efficiency in using small highly functional libraries. These stated techniques rely on a posteriori structural and mechanistic data, yet are thought to enhance the probability of finding viable targets that catalyze biochemical reactions.
Small-Molecule Control of Protein Degradation Using Split Adaptors
This article describes the creation of a small molecule inducer of dimerization system for the degradation of a target protein. Proteins targeted for degradation are brought to the ClpXP protease by an split adapter protein that depends on the small molecule rapamycin for activity. To prove their system works, the authors induced expression of the FtsA protein with IPTG and maintained low levels of FtsA with the addition of rapamycin. A filamentous phenotype was observed when rapamycin was added, a consistent with the absence of FtsA.
The Zipper Model of Translational Control: A Small Upstream ORF Is the Switch that Controls Structural Remodeling of an mRNA Leader
This is an older paper; it is from 2003. However, I have never read it until now. Many current papers state that no one has found a mammalian riboswitch. I knew of one paper in 2009 (previously posted) that did report that they had found a mammalian riboswitch, and to my knowledge this was the only published report of one. Yet, upon further investigation, I found Dr. Maria Hatzoglou web site, where she claimed that she had found the first mammalian riboswitch. I had then followed the citation, and this was the paper. I am very surprised, given the paper's age, that people still claim that there are no endogenous mammalian riboswitches.
This reported riboswitch again does not act like the typical reported prokaryotic switch. In this switch, translation is regulated by what the author calls a zipper model. Breifly, transcribed mRNA is bicistronic. Translation of the upstream gene, causes a conformational change which allows a trans-acting factor to bind and induce translation of the downstream gene.
This reported riboswitch again does not act like the typical reported prokaryotic switch. In this switch, translation is regulated by what the author calls a zipper model. Breifly, transcribed mRNA is bicistronic. Translation of the upstream gene, causes a conformational change which allows a trans-acting factor to bind and induce translation of the downstream gene.
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