In the News!

You may not know this but I've been in the news a bit recently for all the good I do for organisms as small as bacteria and could do for people like you.


Check out this article.


Lohman, Jeremy R., Andrew C. Olson, and S. J. Remington. "Atomic resolution structures of Escherichia coli and Bacillus anthracis malate synthase A: Comparison with isoform G and implications for structure-based drug discovery." Protein Sci. 17.11 Nov. (2008): 1935-45.


Notes on Structure and Reaction Pathway:
This will tell you all you want to know about my structure if you so desire, but I want to focus on some other topics.  The article tells how I am important in the virulence of many bacteria and fungi including Mycobacterium tuberculosis and Candida albicans.  As a part of the glyoxylate shunt, I help avoid the portion of the TCA cycle which gives off carbon dioxide by taking isocitrate directly to malate.  My part of the pathway is the reaction

acetyl-CoA + H₂O + glyoxylate <=> (S)-malate + CoA

The benefit to you people is that you don't have my wondrous enzyme, so even though you are missing out on the benefits you can make drugs to inhibit me so those fungi and bacteria can't enjoy the benefits either.  Taking away my biosynthetic advantages would seriously hamper their virulence, but I think its just jealousy!

One hint to get you started, my A isoform is regulated by acetate and fatty acids while my G isoform is inhibited by glyoxylate, so you may want to start working on their analogs.  Finally, to end on a structural note, my active site is contained within a α8/β8 (TIM) barrel.

More on Virulence and Pathway:

Here is another article which gives more details on the virulent benefits and glyoxylate bypass shunt.

Dunn, M. F., J. A. Ramírez-Trujillo, and I. Hernández-Lucas. "Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis." Microbiology 155 (2009): 3166-75.

 They included this nice figure showing the pathway.

They also go into more detail about the pathway and include some information on how I effect virulence.  According to these researchers, my presence as part of the glyoxylate shunt allows bacteria, fungi, and plants to use two carbon compounds like acetyl-CoA to synthesize four carbon dicarboxylic acids which can then be used for gluconeogenesis or other biosynthetic pathways.  This is essential for survival in the host organisms.  It also allows TCA cycle intermediates to be replenished or increased as necessary.

Some other trivia from this article include the following.  I, as a part of the glyoxylate pathway, am essential for the growth of plant seedlings since I am part of the pathway which allows stored lipids to be converted to carbohydrates.  I also may have functions as an adhesin and biomarker as recent studies into my effect on M. tuberculosis pathogenicity have shown.

One More:

Vanittanakom, Nongnuch, Chester R. Cooper, Jr., Matthew C. Fisher, and Thira Sirisanthana. "Penicillium marneffei Infection and Recent Advances in the Epidemiology and Molecular Biology Aspects." Clinical Microbiology Reviews 19.1 Jan. (2006): 95-110.

This article is about Penicillium marneffei infection, an opportunistic infection in HIV infected patients in  Southeast Asia.  It is a fungal infection which has the advantage of being able to live as a mycelium at 25°C and as a yeast at 37°C which makes it particularly virulent.  It causes fatal systemic mycosis  in those it infects.  My role in the process is in the yeast phase.  Researchers have found that I am up regulated in the first 20 minutes or so of infection suggesting I have a role in infection in the yeast phase.

Some New Pictures

Here are some pictures of me from my trips in various NMR and X-ray spectroscopes.

Here I am sporting some nice Magnesium ions (green spheres)!  You're getting a great view of my active site there in the middle and the picture is color-edited in PyMOL to show off the cartoon structure by secondary structure (PDB:  3CUX).

This is my best piranha pose (sorry you have to imagine the tail).  It features my surface as spheres with the same color scheme as before (PDB:  3CUX).

Here I'm wearing the flashy chainbows color scheme.  My sequence starts in the bottom right with the little tail of dark blue and follows the colors of the rainbow in reverse order of ROY G. BIV to the red helix in the middle.  Trying out the white background so you can see all those colors! (PDB:  3CUX)

Here I am with my twin.  Each of us is featuring two Mg ions with an oxalate ion bound to the central ion, as well as a CoA.  The color scheme is by chain showing that we are each one chain. (PDB:  3CV2)

This picture is an attempt to show off the residues around the active site.  The Magnesium ion has been colored orange and the green atoms are carbons.  The rest follows the traditional color scheme for elements. (PDB:  3CUX)