“I didn’t hear about this experiment until I was a freshman at Brown”

At the Herbert Tabor Research Award Lecture at the American Society for Biochemistry and Molecular Biology meeting, in his talk “Chaperonin-mediated protein folding”, Prof. Arthur Horwich of Yale University and the Howard Hughes Medical Institute opened by regaling us with the story of the famous experiment by Christian Anfinsen.  The hypothesis was that all of the information required for a protein to fold into its three-dimensional shape was encoded in the amino acid sequence.  He tested the hypothesis by treating the protein with urea and beta-mercaptoethanol (BME), chemicals that cause the protein to unfold, then he slowly removed the urea and BME, and amazingly he recovered the protein’s activity, meaning that it had folded correctly.  This is amazing because the number of possible arrangements the protein could assume is huge, and yet it was able to find the right one.  The experiment is elegant, and it won a Nobel Prize in 1972.

It’s a common story to use when beginning a talk on protein folding, but I was more interested by what he said next: “I didn’t hear about this experiment until I was a freshman at Brown”, as if he had expected to have heard about it earlier.

I think this story illustrates the gulf between what scientists expect the public to know and what the public actually knows.  I went to an excellent high school, but my ninth-grade biology class didn’t really discuss biochemistry at a molecular level, and for pretty fair reasons: we didn’t have chemistry until tenth grade, so I’m not sure what would have been gained by talking about the fact that proteins are made of amino acids and the protein folding problem.  In Advanced Placement Chemistry in eleventh grade, we spent a good deal of time on intermolecular interactions, so we probably could have applied those principles to proteins, but it was a chemistry class, not a biochemistry class, so we didn’t.  So even as a definitely more-educated-in-chemistry-than-average student, I, as Prof. Horwich, entered college having never heard of the Anfinsen experiment, or indeed of protein folding.  We scientists would do well to remember that when trying to communicate with the public.

word of the day: actinic

The word of the day is actinic:

Etymology:  < ancient Greek ἀκτῖν-, ἀκτίς ray (see actino- comb. form) + -ic suffix.

1. Of or relating to actinism; (of light) having the ability to cause a chemical change; having a relatively high ultraviolet content; = photogenic adj. 1.
2. Esp. of a medical condition: produced or caused by the action of light; = photogenic adj. 2. (OED)

"Photoaffinity probes need to fit the following requirements: the probe must be chemically inert in the absence of actinic light; the photophore has to be activated under mild conditions and its activation must not damage the biosystem and its components; the lifetime of the excited state of the label has to be shorter than the lifetime of a ligand-receptor or another complex under study; the activated probe has to nonspecifically react with any neighboring group, including saturated CH-chains of lipids and nonpolar amino acid residues, with production of a tight covalent bond; the photophore must not induce significant disorders in the biosystem organization; the photophore introduction into the initial substance molecule must not considerably decrease the biological activity; the probe has to contain a radionuclide with a sufficiently high specific activity or an additional label attached through an elongated linker; the probe has to be available."

 - E. L. Vodovoza, "Photoaffinity Labeling and Its Application in Structural Biology", Biochemistry (Moscow) 72:1 (2007)

Molecule of the day: bicinchoninic acid

The molecule of the day is bicinchoninic acid:

It apparently chelates Cu(I) ions to produce a  purple product.  Peptide bonds can apparently reduce Cu(II) ions to Cu(I) ions, so bicinchoninic acid can therefore be used to assay the amount of protein in a solution, as in this paper.

Molecule of the day: phenylglyoxal

The molecule of the day is phenylglyoxal:

(PubChem)

It can be used to covalently modify arginine residues, as such:

(source)

Molecule of the day: ninhydrin

The molecule of the day is ninhydrin (image source):

It's used to colorimetrically detect primary amines, as such (source):

The molecule of the day is dithiobis(2-nitrobenzoic acid):

(PubChem)


It reacts with sulfydryl groups (in proteins, for example) to produce an anion, which can be measured colorimetrically, as such (image source):

The molecule of the day is homoserine:

It is produced when cyanogen bromide is used to cleave a protein at a methionine, as shown here: