Kritzer Feed

Rocket enzyme, burnin’ down its fuse in microscopes

February 5, 2015 · No Comments


rocket-powered enzyme

Enzymes don’t change the thermodynamics of a reaction (how energetically favorable it is), they just provide a lower-energy path from reactants to products.  Since most biochemical reactions release heat (a major component to the favorable free energy), most enzymes produce little bursts of heat when they catalyze a reaction.  This heat can be measured using enzymes in a test tube, and it all matches theory just fine.

But what happens to that heat at the molecular level?  Recall that heat is a measure of molecule movement — water (or any other molecules) at a higher temperature have a faster average speed as they move around in solution (as they diffuse).  So if an enzyme catalyzes a reaction, the heat produced by that reaction will make the water molecules nearby move.  This will form an “acoustic wave” just like you clapping your hands loudly in an empty room, or you kicking hard underwater.  This wave pushes in all directions, including on the enzyme itself.  Result?  The enzyme moves a little bit in the other direction!  The enzyme quite literally rockets forward due to the heat released when it catalyzes a chemical reaction!  Just, you know, much slower than an actual rocket.

This is what scientists thought might be happening for some time.  Recently, groups at UC Berkeley and Indiana University managed to use a technique called single-molecule fluorescence correlation spectroscopy to monitor the diffusion of individual enzymes, and showed that the enzymes’ movement through water was directly related to how quickly they were catalyzing their reactions.  They showed this for four different enzymes, and ruled out other possible explanations for this molecular movement.  So the above model seems to be correct!  Whether this is something important for the function of enzymes in living cells is hard to know (maybe it allows enzymes to move away from products and towards other substrate molecules?), but it is surely under further investigation…

See the commentary here, then graduate to the full article here!

-Prof. Kritzer

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SnapShot: GPCR-Ligand interactions

January 30, 2015 · No Comments


In Chem171 this semester we will not be getting to signaling pathways — not because they aren’t important (quite the contrary!!!) but so we can spend a lot of time on them in Chem172.  Whether or not you are taking the second semester, the field of “signal transduction” has produced some of the most interesting and important biological findings (and pharmaceuticals!) in the past 50 years.  Chapter 12 in Lehninger is a fantastic and comprehensive overview that you will use repeatedly in other classes and in any work you do related to biology and medicine in years to come!

In this post, I point you to a poster-size “SnapShot” of interactions between an important cell surface receptor family and their ligands.  These receptors, called G-protein-coupled-receptors or GPCRs, are seven-helix transmembrane proteins that bind a molecule on the outside, then rearrange to cause chemical changes on the inside.  This allows the cell to detect and respond to the presence of an extracellular molecule.  GPCRs mediate signaling in response to everything from opioids to epinephrine (adrenaline) to serotonin.  GPCRs like rhodopsin even form the basis of vision, allowing conformational changes in the receptor upon absorbance of light!!

SnapShots are poster-size graphics produced by Cell.  Have fun perusing the gallery while you’re there!

-Prof. Kritzer

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A new era of protein design

January 24, 2015 · No Comments



As the above xkcd cartoon implies, the “protein folding problem” has been referenced for many decades as a near-unsolvable problem.  Despite the daunting task of finding a protein’s lowest-energy fold given only its sequence, several labs have made considerable strides in the last 5-8 years.  Chief among these labs is the Baker lab at U. Washington, who have designed a computational algorithm called Rosetta that combines information from existing protein structures (empirical data), physics-based calculated energies from noncovalent interactions, and random search algorithms (called “Monte Carlo” algorithms) to search for well-folded structures.

This has led to a new era of protein design, with several examples of new protein folds designed from scratch, and new ligand-binding proteins and enzymes.  In 2012, the Baker lab distilled some general findings for small protein domains, describing how to fold small assemblies of beta-sheets and alpha-helices (paper and summary).  For those of us who were originally taught that the protein folding / protein design problem was unlikely to be solved in our lifetime, this is heady stuff!!

And, of course, if you’d like to participate in the effort to solve novel protein folds, you can register with FoldIt to contribute your own mad protein folding skillz!!

-Prof. Kritzer

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Protein Folding update for 2015

January 14, 2015 · No Comments

The Nature of Protein Folding Pathways

Fig. 1.

S. Walter Englander and Leland Mayne.  Proc. Nat. Acad. Sci. (2014) 111, 15873.


This is an excellent review that provides historical context for not just the central concepts of protein folding, but also the specific experiments and experimental setups that were key for working them out.  It also gives a modern view of protein folding and what questions remain to be answered.

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