NDLI: Crystal Structure of Toxoplasma gondii Porphobilinogen Synthase

Content Provider	PubMed Central
Author	Jaffe, Eileen K. Shanmugam, Dhanasekaran Anna, Gardberg Dieterich, Shellie Sankaran, Banumathi Stewart, Lance J. Myler, Peter J. Roos, David S.
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.
Related Links	http://dx.doi.org/10.1074/jbc.m111.226225
Ending Page	15307
Page Count	10
Starting Page	15298
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	17
Volume Number	286
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2011-04-29
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Crystal Structure of Toxoplasma gondii Porphobilinogen Synthase INSIGHTS ON OCTAMERIC STRUCTURE AND PORPHOBILINOGEN FORMATION

Plastid-associated Porphobilinogen Synthase from Toxoplasma gondii

Plastid-associated Porphobilinogen Synthase from Toxoplasma gondii KINETIC AND STRUCTURAL PROPERTIES VALIDATE THERAPEUTIC POTENTIAL

Dissecting the molecular assembly of the Toxoplasma gondii MyoA motility complex

Primary structure of the dihydrofolate reductase-thymidylate synthase gene from Toxoplasma gondii.

Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.

Allosteric Inhibition of Human Porphobilinogen Synthase*

Allosteric inhibition of human porphobilinogen synthase.

Crystal Structure of Human Spermine Synthase

Crystal Structure of Toxoplasma gondii Porphobilinogen Synthase

Similar Documents

Crystal Structure of Toxoplasma gondii Porphobilinogen Synthase INSIGHTS ON OCTAMERIC STRUCTURE AND PORPHOBILINOGEN FORMATION

Plastid-associated Porphobilinogen Synthase from Toxoplasma gondii

Plastid-associated Porphobilinogen Synthase from Toxoplasma gondii KINETIC AND STRUCTURAL PROPERTIES VALIDATE THERAPEUTIC POTENTIAL

Dissecting the molecular assembly of the Toxoplasma gondii MyoA motility complex

Primary structure of the dihydrofolate reductase-thymidylate synthase gene from Toxoplasma gondii.

Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.

Allosteric Inhibition of Human Porphobilinogen Synthase*

Allosteric inhibition of human porphobilinogen synthase.

Crystal Structure of Human Spermine Synthase

Crystal Structure of Toxoplasma gondii Porphobilinogen Synthase