Thursday, March 10, 2011

Crystal structure of Toxoplasma gondii porphobilinogen synthase: insights on octameric structure and porphobilinogen formation

J Biol Chem. 2011 Mar 7. [Epub ahead of print]

Crystal structure of Toxoplasma gondii porphobilinogen synthase: insights on octameric structure and porphobilinogen formation

Jaffe EK, Shanmugan D, Gardberg A, Dieterich S, Sankaran B, Stewart LJ, Myler PJ, Roos DS.

Fox Chase Cancer Center, United States;

Abstract
Porphobilinogen synthase (PBGS) is essential for heme biosynthesis, but the enzyme of the protozoan parasite Toxoplasma gondii (TgPBGS) differs from that of its human host in several important respects, including subcellular localization, metal ion dependence, and quaternary structural dynamics. We have solved the crystal structure of TgPBGS, which contains an octamer in the crystallographic asymmetric unit. Crystallized in the presence of substrate, each active site contains one molecule of the product porphobilinogen. Unlike prior structures containing a substrate-derived heterocycle directly bound to an active site zinc ion, the product-bound TgPBGS active site contains neither zinc nor magnesium, placing in question the common notion that all PBGS enzymes require an active site metal ion. Unlike human PBGS, the TgPBGS octamer contains magnesium ions at the intersections between pro-octamer dimers, which are presumed to function in allosteric regulation. TgPBGS includes N- and C-terminal regions that differ considerably from previously solved crystal structures. In particular, the C-terminal extension found in all apicomplexan PBGS enzymes forms an intersubunit β-sheet, stabilizing a pro-octamer dimer and preventing formation of hexamers that can form in human PBGS. The TgPBGS structure suggests strategies for the development of parasite-selective PBGS inhibitors.

PMID: 21383008 [PubMed - as supplied by publisher]

3 comments:

Donate Plasma said...
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Emily Sherman said...

Hey, great article! Did you know that there are actually biotech companies that develop drugs, vaccines, and treatments need people with recent or recurring toxoplasmosis infections to donate plasma? They actually will pay money, like $800 or more to each donor, or will give that money to a charity of your choice for each plasma donation. You can check it out at www.idonateplasma.com...love the Anti-Toxo title. I will definitely be checking back to see more of your posts in the future.

Imgenex said...

Here you provide contents about the crystal structure of Toxoplasma gondii. It is an obligate intracellular parasite of warm blooded animals, including humans, and belongs to the phylum Apicomplexa, which includes other medically relevant organisms such as plasmodium falciparum and cryptosporidium parvum. Thanks a lot...

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