Microbiology at Atomic Resolution --- Update 4/27 Welcome to Micro/BMC 668 -- Spring 2009 Check this schedule each week; it evolves. Week 1, 1/20 + 1/22 Protein Structure: History, Building Blocks and Tools. Week 2, 1/27 + 1/29 DNA binding specific and non-specific. DNA structure (book), CRP (Parkinson), IHF (Rice) Crystallography Concepts I: data and structure quality; structure factors and electron density Week 3, 2/3 + 2/5 PBPs/Quorum Sensing. MBP (Quiocho), LuxP (Hughson) Crystallography Concepts II (Book chapter reading too): Phasing: the Patterson function and its application to MIR and MR Week 4, 2/10 + 2/12 2-Component regulatory systems CheY (several papers) Signal transduction with RR; DNA-bound NarL Crystallography Concepts III (Scattering) Week 5, 2/17 + 2/19 Outer Membrane Porins and Inner Membrane Helices General features (book) Maltoporin (Schirmer, ktf) K+ channel (Jiang, bg) Week 6, 2/24 + 2/26 Transcription Mike Frazier (evolution, Cramer et al.) Valerie Davis (polio 3C, Thompson et al.) Week 7, 3/3+3/5 Translation Low resolution studies of the ribosome (ktf) Mechanisms of fidelity in translation (Ogle et al., Jared Winkelman) Week 8, 3/10+3/12 Cell Wall Biology and Antibiotics Beta lactamase inhibitors (Sarah Marcus) Inhibition of fatty acid synthesis (Ryan Peterson) Spring Break 3/17+3/19 Week 9, 3/24+3/26 Protein Secretion Review of structure themes (ktf) SecY-dependent protein secretion (van den Berg et al., Bryan Sibert) Week 10, 3/31 + 4/2 Metabolism John Oswald (detoxification; aldo-keto reductases; Kozma et al.) Norbert Tavares (Fe regulation via IRP/aconitase; Walden et al.) Week 11, 4/7 + 4/9 Phage/Virus/Prion Structures Laura Franz (viruses, including icosahedral symmetry, Reddy et al.) Melanie Spiro (prion/amyloid structures; Bayley et al. and Meier et al.) Week 12, 4/14 + 4/16 ATPases, Motors and Motility Lauren Palmer (F1F0 ATPase, Bowler et al.) Basu Bhattacharyya (RecQ, Bernstein et al.) Week 13, 4/21 NO CLASS + 4/23 Critical Crystallography Ktf (ABC Transporter retractions, Jeffrey 2009) Week 14, 4/28 +5/3 Structure Assessment and Using 3D Predictions Tuesday --- ABC Transporters (Locher and Rees) Thursday --- structure validation tools (and homology models if time) Week 15, 5/5+ 5/7 Receiving and releasing light – Rhodopsin, BLUF, LOV, PHY, GFP KTF overview and phytochromes Chris Lennon (rhodopsin) Micro/BMC 668 Syllabus Details Instructor Katrina Forest, 6552 MSB, x5-3566, forest@bact.wisc.edu. The best time to talk to me is right after class. Otherwise, I have an open-door policy but you might want to e-mail or call me first to make sure I'll be around. General topics to be covered 3-dimensional crystal, nuclear magnetic resonance, or electron microscopy structures will be the basis for discussions of molecular processes that are critical to microbiology in particular, but have direct relevance to all biological systems. By studying selected proteins and nucleic acids in detail we'll learn how specific problems are solved with given protein architectures and chemistries as well as more generally how successful themes of protein structure are modified and recycled. There will be two meetings each week, both in the Molecular Modeling classroom in MSB. We will make extensive use of computer graphics programs (especially PyMol) for 3-D emphasis as well as of databases and programs available on the World Wide Web for retrieving and manipulating structural information. Grades will be based in equal thirds on (1) preparedness for and participation in class (2) scores on quizzes and assignments and (3) your in-class presentation (see next page for details). There is no final exam (even though one is listed in the exam schedule). Text Book/References Original journal articles available on the web or handed out as xeroxes. Introduction to Protein Structure, Branden and Tooze. 2nd edition (1999) Gardner Press. (Available at the University Book Store) Additional texts you might find useful (some in Steenbock; I have them; or try used on-line): Crystal structure analysis: a primer, Glusker and Trueblood. 2nd edition (1985) Oxford University Press. Introduction to Macromolecular Crystallography, A. McPherson. 2002, Wiley and Sons. Proteins Structure and Function David Whitford, 2005, Wiley and Sons On line resources you may want to make use of: # RasMol. # Swiss PDB-Viewer. # Molprobity # Dyndom # SwissModel Student-led Discussion The idea behind the student-led discussion is for each of you to critically dig through some primary literature, understand the background and important questions that lead up to a structure, and thoroughly master the information in a few papers on a protein or system you find particularly interesting. (So far sounds like the goal behind all of the classes). THEN, you need to present this information to your classmates and lead a discussion that hopefully brings them (and me) to a similar level of understanding. The mechanics of this are as follows: 1. Consider the general syllabus outline for the course, and select a topic you're interested in. Let me know as soon as possible but no later than February 4th. In class on the 5th we’ll slot everyone into the calendar. Then, on your own and/or with input from me, choose a few appropriate references, and write up a short (less than one page) proposal for your class period. YOU MUST DO THIS, IN WRITING, BY FEB. 11th. If you are most interested in a topic coming up early in the semester you should be sure to let me know and write your proposal sooner. If done well, this can become a rough draft of your study guide. There are some weeks for which I have specific papers in mind already and others that are more open. If your interests overlap with a week the papers are already set for, that's fine! 2. Prepare yourself. Read the papers, survey the literature, understand the background, and plan your approach for leading the discussion in class. Come talk to me IN PERSON at least two weeks before your class period (sooner is fine), and provide the pdf files for me to put up on the class web page. I suggest one primary literature paper and possibly one review article. (Remember your classmates will be reading papers for other presentations as well). *** As part of this preparation you must also give to me a short (2 pages max) write-up, which should take the form of a STUDY GUIDE that you can hand out as well to the class. Somehow by reading this I should know that you understand the material and that you are ready to lead the class. For example, I imagine (I) a couple paragraphs of background to put your protein in context with one or more suggested review articles or book chapters (DO NOT just list every paper you know of on the subject, but be selective), (II) the underlying take home points of the structures and (III) study questions for in-depth thinking. You should be sure you can answer the latter. **** 3. "Display items" Make a model and/or a movie to help your presentation. We have in the Biotechnology New Media Center a 3D printer which can make physical models of proteins using a set of Pymol instructions. In addition or as an alternative, you can use Pymol to make a high quality movie. 4. Lead the class on the appropriate day. In addition to the model or movie above, take advantage of any multimedia you want to make your points; whiteboards, overheads, lecturer's station in classroom, PyMol scripts, etc. If you need help, ask me. For example, I could put something you give me up on the class web site. Remember to try to put the discussion in the context of what we may have learned already. Conserved folds? Similar active site geometries? Also remember that you will know the system and the structure inside out and your challenge is to help us learn about it, not only to show us how much you know. Have fun and don't freeze up. By now you know what you're talking about and your job is to facilitate a discussion. To listeners/class members: You have a job as well, which is to come prepared to class and help your colleague by answering and asking questions. Hostility is not a good idea, but it's certainly fine to ask for clarification if you don't understand something. You will be asked at the end of class to fill out a short constructive evaluation form.