Monday's Molecule #133: Winner?

 
If you look closely at the two molecules (below) you'll see that the one on that left has an extra bit of polypeptide chain compared to the one on the right. Some part of the protein has been removed to create a smaller version.

This should have reminded you of the kinds of reactions that take place when zymogens are cleaved to produce an active enzyme. This is pepsin, the classic example of such a reaction.

Pepsin is a protease—an enzyme that degrades proteins to small peptides in your stomach during digestion. It is initially synthesized as an inactive precursor called pepsinogen (left). When pepsinogen is secreted into the stomach it is inactive until it is cleaved in an autocatalytic reaction stimulated by HCl secretions. The blue bit sticking out on the right of the figure is chopped off, uncovering the active site in the large cleft in the right center of the molecule. This form of activation makes sense since it's not a good idea to have an active protease in the cytoplasm of your cells.

Pepsin—the protein ferment—has been known since the 1830s. At the end of the nineteenth century Ivan Pavlov carried out a series of experiments in an attempt to understand how digestion in the stomach worked. He learned that the initial secretion containing pepsin was inactive until it was combined with a separate secretion.

Pavlov received the Nobel Prize for his work on digestion.

Only one person guessed the molecule but that person did not figure out that Pavlov was the first one to deduce that digestive enzymes were initially produced in an inactive form. There is no winner this week! Even the "regulars" were stumped this time.

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Here are two different versions of the same enzyme. One of them is the active form and the other is inactive. You should identify the enzyme and briefly explain the difference between the two structures.

This is a famous enzyme whose activity was first detected over one hundred and fifty years ago. The Nobel Laureate associated with the two forms shown above is also very famous. He was the first person to discover that there were active and inactive forms of the enzyme and to provide a reasonable explanation. The Nobel Prize was awarded for many other contributions to the field and not just for this discovery. However, the fact that he is better known for other studies should not detract from his significant contributions to biochemistry.

The first person to identify the molecules and the Nobel Laureate, wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only six ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey, Alex Ling of the University of Toronto, and Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

Comments will be blocked for 24 hours.

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