I realized that there is no information in our COURSE MATERIALS on the amino
acid selenocysteine.
Because
a) I am particularly interested in the study of proteins that contain this
amino acid;
b) would like to increase my understanding of the properties of
selenocysteine;
c) and would like you to know about another amino acid,
I thought of asking for your attention and possibly start a discussion on the
21st amino acid selenocysteine (Sec, U).
I plan on making a html document on selenocysteine (I know more about this
amino acid than I do about Internet and so it may take some time before I am
done...) but would like to have your view and feedback on a number of
questions that I will formulate at the end (if you allow me to...).
But first, here are a few points about selenocysteine (Sec, U) that I need to
introduce to you:
1. Selenocysteine is identical to cysteine except that the sulfur atom has
been replaced by selenium.
2. This amino acid is co-translationally incorporated into nascent
polypeptides using UGA codons (commonly used as STOP or termination codons).
3. For the incorporation of Sec to occur there is a requirement for the
existence of specific secondary structures in the mRNA that interact with a
specific elongation factor that in turn interacts with specific tRNAs
complementary to the UGA codon, which are charged with selenocysteine.
4. Previously described selenoproteins (proteins that contain selenocysteine)
include bacterial enzymes involved in oxidation/reduction processes (formate
dehydrogenases, hydrogenases and glycine reductase) and a number of eukaryotic
proteins:
- glutathione peroxidases (involved in oxidation-reduction reactions),
-iodothyronine deiodinases (which metabolize thyroid hormones),
- selenoprotein W and selenoprotein P (both of unknown function),
-and a selenoprotein of the sperm mitochondrial capsule +
-another protein that I am working on right now but, due to the fact that I
work in a company, I unfortunately can not identify at the moment.
I still lack knowledge to understand some of the aspects of the biochemistry
of this amino acid that have a lot to do with the presence of the selenium
atom in place of sulfur and would like to have your comments on the following
points- this will obviously increase the quality of the page on selenocysteine
for which I am offering to organize the material of this discussion and the
progress of my own research:-):
1 - What will be the consequences in terms of amino acid properties (size,
hidrophobicity, etc.) that you expect to result from the replacement of sulfur
by selenium?
2 - Why is that the placement of Sec at the active site of a protein results
in the observation that selenocysteine-containing enzymes are hundreds to
thousands of times more active than their cysteine-containing counterparts)?
3- Could selenium participate in the formation of Se-Se bonds similar to the
S-S bonds? Please explain your reasons.
4- What happens to the selenium atom that is present at the active site of
selenoenzymes during and after an oxidation-reduction reaction?
5- Can anyone help me to build an image for selenocysteine in Rasmol similar
to the ones that are available at our site for all the other amino acids?
Please forgive me if I went too far in trying to start this discussion but I
thought that maybe it would be important not to leave an amino acid behind. I
know that selenocysteine for some reason is not yet in most of the
biochemistry text books and, on the other hand, working on this, I would
appreciate any feedback from all of you on the biophysical, biochemical and
whatever else properties of this "Seweet" amino acid...
Here are a few reviews on selenocysteine and its incorporation into proteins
that you may want to take a look at:
Berry, M.J. & Larsen, P. R. Biochem. Soc. Trans (England) 21, 827-832 (1993).
Stadtman, T. C. Annu. Rev. Biochem. 59, 111-127 (1990)
Bock, A. et al. Mol. Microbiology 5, 515-520 (1991).
Thank you all very much.
M. Jorge Guimaraes, Guanine Group
DNAX Research Institute
901 California Avenue, Palo Alto, CA 94304, USA.
Tel (415) 496 1172/253
Fax (415) 496 1200
guimaraes@dnax.org
mjorge@best.com