Enzymes differ from other catalysts in the exceptional substrate selectivity they exhibit. However, the active sites of related enzymes are often very similar, even though different substrates are acted upon (for example in the superfamily of cytochrome P450s). How does a given enzyme preferentially bind a particular substrate? In a new paper appearing in the jounal Metallomics, Chemistry grad student Marina Dang and Profs. Susan Sondej Pochapsky and Thomas Pochapsky use nuclear magnetic resonance (NMR) to identify a helical structure remote from the active site of the enzyme cytochrome P450cam that is responsive to changes in substrate. They propose that this helix can adjust the position of residues that contact substrate in the enzyme active site, much like the spring that holds batteries in place against electrical contacts in a flashlight.
Brandeis undergraduates can take a peek at what the future might hold for them. Polina Ogas ’07 (BS/MS, Biochem), now in the MD/PhD program at Harvard Med, discusses the details on the Harvard Med Girl blog.
The 2011 recipients of the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science are C. David Allis (Rockefeller Univ.) and Michael Grunstein (UCLA) for their discovery that histones and histone acetylation directly regulate transcription. There will be lectures and an award ceremony at Brandeis University on April 14, 2011 at 3:30 pm in the Carl J. Shapiro Theater, Shapiro Campus Center
C. David Allis
|Beyond the Double Helix: Varying the ‘Histone Code’|
(Distinguished Professor, Department of Biological Chemistry, University of California, Los Angeles )
|Towards histone function|
A reception will follow in the Shapiro Science Center Atrium for all attendees of the talk, from roughly 5:30 until 7 pm.
Science and technology moves forward at a very rapid pace. Those who don’t continue to read the literature become outmoded. What kinds of learning activity help students develop the necessary skills, and habit, for reading science?
In the dissertation work of Johann Larusson, my lab began to develop a co-blogging environment that already has been adopted in several different classes at Brandeis. Student co-blogging is a text-based online student community that supports students as they learn to read and write science.
In the co-blogging environment, each student has a blog. The blog is composed of multiple posts written by the blog owner. Students can read each other’s blog posts and comment on them. Student co-blogging has tremendous potential as a learning activity. It continues to be a research topic for my lab.
Co-blogging enables students to move beyond just rereading their notes and assigned readings as a way to learn material. Students have the opportunity to review, rethink, articulate, explaining in their own words what is signiﬁcant about the material, making “common” sense of the causal relations among the different elements of the course content. The discussions that naturally emerge expose the students to alternate ways of “seeing” and “constructing” what is signiﬁcant and why, allowing students to collaboratively work through arguments and trade-offs, weighing and comparing different explanations and justiﬁcations. To a greater or lesser degree each of these elements has developed in the courses I teach.
During the semester, there is an aggregation of content in the blogosphere. Topics and themes introduced at the beginning of the semester persist in the blogosphere and can be revisited and further developed as they again become relevant. The aggregated content of the blogosphere can be exploited for other learning activities like constructing arguments, summarizing the literature, writing papers, or preparing for exams.
Each post in the blogosphere is tagged by the student from a selection of pre-deﬁned topics. These tags help students to navigate the blogosphere. Students also receive daily email newsletters that summarize the online co-blogging activity of the class in the previous 24 hours. Students can use links in the newsletter to directly navigate to posts or comments on the blog site that are of particular interest.
The co-blogging environment provides some visualizations for the teacher and students that represent student activity level, balance of participation, and other aspects of the blogosphere. The visualization shown below helps students and teachers locate discussions within the blogosphere.
More papers with Brandeis authors (boldface) and/or from Brandeis graduates (bold italics) that we noted online in the last month, but didn’t have time to discuss.
- Bosco DA (Ph.D. ’03), Morfini G, Karabacak NM, Song Y, Gros-Louis F, Pasinelli P, Goolsby H, Fontaine BA, Lemay N, McKenna-Yasek D, Frosch MP, Agar JN, Julien JP, Brady ST, Brown RH, Jr. Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nature Neuroscience. 2010;13(11):1396-403. (see also http://www.umassmed.edu/news/articles/2010/possible_ALS_treatments.aspx)
- Amelung C. First results from the ATLAS muon spectrometer optical alignment system. Nucl Instrum Meth A. 2010;623(1):388-90.
- Vega A, Luther JA, Birren SJ, Morales MA. Segregation of the classical transmitters norepinephrine and acetylcholine and the neuropeptide Y in sympathetic neurons: modulation by ciliary neurotrophic factor or prolonged growth in culture. Developmental Neurobiology. 2010;70(14):913-28.
- Li X, Li J, Gao Y, Kuang Y, Shi J, Xu B. Molecular Nanofibers of Olsalazine Form Supramolecular Hydrogels for Reductive Release of an Anti-inflammatory Agent. J Am Chem Soc. 2010.
In this week’s on-line issue of the Proceedings of the National Academy of Sciences (PNAS), Brandeis researchers Jerry H. Brown, V. S. Senthil Kumar, Elizabeth O’Neall-Hennessey, Ludmila Reshetnikova, and Michelle Nguyen-McCarty ’10, together with Professors Andrew Szent-Györgyi and Carolyn Cohen, and Brookhaven National Laboratory researcher Howard Robinson, reveal the existence of a pair of major new hinges in the muscle protein myosin.
Muscle consists of myosin-containing thick filaments with projections, i.e. myosin heads, that exert force on actin-containing thin filaments during contraction. Previous crystal structures of the myosin head from bay scallop striated muscles and vertebrate muscles have already shown how this motion is produced by the amplification of small conformational changes about hinges in the motor domain (MD) by the so-called lever arm, which consists of the converter and elongated light chain binding domain (LCD). Just like a baseball bat or other lever arms we are all familiar with in the “real world”, this LCD of myosin has appeared to be relatively rigid in these crystal structures, as it needs to be to transmit force effectively. But it has also long been expected that in muscle the myosin head, including its lever arm, is likely to contain elastic elements so that force can be produced under various strains.
(Left) Schematic of a myosin molecule and (right) the two conformations of the heavy chain portion of the LCD.
The Brandeis researchers originally set out to crystallize a myosin LCD corresponding to that from the catch muscle of sea scallop because it contains a specialized sequence whose structure was predicted to give insight into how muscle contraction of smooth muscles is turned on and off. Remarkably, however, as described in the PNAS article, this LCD forms two different conformations in the crystal, about mechanically linked hinges in the part of the lever arm distal from the motor. For the first time — and quite unexpectedly— a potential major elastic element in the lever arm has been visualized at atomic resolution, one that allows the length of the lever arm to change by about 10%. Sequence comparisons strongly suggest that these specific hinges are likely to be found in the lever arms of all muscle myosins. These comparisons also indicate differences in the degree of flexibility about these hinges in the different myosins, perhaps helping to account for the different properties (e.g., speed of contraction) of different types of muscle.
This result may also be important for mechanical engineers. In 2009, one of the authors (JHB) wrote an article in American Scientist that expands the concept of biomimicry by describing potentially novel joints, switches, and other mechanical designs that can be derived from the structures of various proteins. The current results in the PNAS seem to add one more. As described by Olena Pylypenko and former Brandeis researcher Anne Houdusse in a commentary scheduled to accompany the print version of the PNAS article, the motion about the hinge of the myosin LCD resembles the motion of a foot relative to a leg about an ankle. A lever “arm” that can extend or compress about an “ankle” may thus be one more novel mechanical design that nature can teach us about.
The 5th Annual Quantitative Biology Bootcamp will be held on January 16 & 17, 2011. Paul Miller will preside over the 2nd annual QB Computational Challenge: When space trumps time: modeling dynamic spatial patterns with Matlab. This year’s panel discussion topic is “Writing interdisciplinary papers. What to do. What not to do.” We’re delighted to announce the HHMI Interfaces Scholar award went to Adelajda Zorba (Kern lab). Adelajda was selected from among several exceptional submissions this year. The topic is HIV-1 assembly.
Members of the Brandeis community are invited to attend. If you are interested, please contact Trisha Murray no later than Jan. 4, 2011.
2010 Beckman Scholar Philip Braunstein ’12 discusses his research project in the Hedstrom lab at the last class meeting of Organic Chemistry CHEM 25a. Training the scholars in communicating science and improving the visibility of undergraduate research are key components of the Beckman Scholars program.
Photographs by Nathaniel Freedman