© 2000 Rainer Glaser. All rights reserved.
The University of Missouri at Columbia
Chemistry 212 - Organic Chemistry II - WS00


Pointers on Web Destinations

Friends & Students!

On occasion, I will be pointing out a few WWW links to you. Many of these links, and many more, can be found in the "Web Destinations" section of the course web site.

We talked about penicillin in lecture. This most famous beta-lactam. The News Item associated with Chapter 21 also addressed issues related to antibiotics and penicillin. We talked about the mechanism of action of penicillin and we saw this mechanism "at work" watching the movie of the bacteria dying a horrible penicillin-caused death. Bacteria have cell walls and penicillin interfers with the formation of cell walls. We discussed briefly the chemistry of this mode of action. Some of the enzymes involved in cell wall formation react with the beta-lactam. By adding the penicillin to the enzyme, the enzyme becomes unable to perform its function. There was some confusion as to whether the beta-lactam is attacked by an amine or by an alcohol, that is, whether the lactam-opening is a transamination or whether a strained amide is converted into a strain-free ester. I have since looked into this matter and here is what I found.

Many people studied the mechanism of action of penicillin and one of the leaders in the field was (and still is) Dr. Jack Strominger of Harvard University. (It just so happens that I met Dr. Strominger last Wednesday, March 8, when he was on the MU campus to present a lecture as part of Molecular Biology Week. I received the Sigma Xi Award and the award was given just prior to Strominger's lecture.) In any case, Strominger wrote an article in 1973 on "The Actions of Penicillin and Other Antibiotics on Bacterial Cell Wall Synthesis" (Hopkins Med. J. 1973, 133, 63-81) and one of the 212 students, Ryan Lehman, brought this article to my attention. "Transpeptidases" are the key enzymes.

In 1973, of course, there were no X-ray structures of enzymes. But that situation has greatly changed in the 1990's. The determination of the crystal structure of an enzymes is now almost routine. Take a look at some enzyme structures at the Protein Data Bank. Go to PDB and click on "SearchLite". Type "Transpeptidase" in the search field and return (or click on the search button). You will see a list of entries and the first one looks like this
1CEF               Deposited: 12-Jan-1995  Exp. Method: X-ray Diffraction
                   Resolution: 2.04  { EXPLORE }
Classification     Hydrolase-Transpeptidase
Compound           Mol_Id: 1; Molecule: D-Alanyl-D-Alanine Carboxypeptidase
                   Transpeptidase; Chain: Null; Synonym: Penicillin 
                   Target; Ec: 3.4.16.4
Click on { EXPLORE } and look around. Try the "View Structure" option; the first time you go there, you will be "amazed". Then try the "Medline" link. Read the abstract to the article by "Kelly, JA, et al."

Well, now you know: This transpeptidase contains a serine in the active site, Ser62, and this serine binds penicillin. Serine, of course, is an amino acid with a -CH2-OH side chain. Das also ist des Pudel's Kern!

As always, enjoy, RG.