3OBK

Crystal structure of delta-aminolevulinic acid dehydratase (porphobilinogen synthase) from toxoplasma gondii ME49 in complex with the reaction product porphobilinogen

Summary for 3OBK

• Entry DOI: 10.2210/pdb3obk/pdb
• Descriptor: Delta-aminolevulinic acid dehydratase, MAGNESIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: ssgcid, structural genomics, seattle structural genomics center for infectious disease, dehydratase, lyase
• Biological source: Toxoplasma gondii ME49
• Total number of polymer chains: 8
• Total formula weight: 320087.94

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2010-08-06, release date: 2010-09-15, Last modification date: 2023-09-06)

Primary citation

Jaffe, E.K.,Shanmugam, D.,Gardberg, A.,Dieterich, S.,Sankaran, B.,Stewart, L.J.,Myler, P.J.,Roos, D.S.
Crystal Structure of Toxoplasma gondii Porphobilinogen Synthase: INSIGHTS ON OCTAMERIC STRUCTURE AND PORPHOBILINOGEN FORMATION.
J.Biol.Chem., 286:15298-15307, 2011

PubMed 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.

PubMed: 21383008
DOI: 10.1074/jbc.M111.226225

Experimental method

X-RAY DIFFRACTION (2.5 Å)