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'''STRUCTURE OF 2C-METHYL-D-ERYTHRITOL-2,4-CYCLODIPHOSPHATE SYNTHASE''' | '''STRUCTURE OF 2C-METHYL-D-ERYTHRITOL-2,4-CYCLODIPHOSPHATE SYNTHASE''' | ||
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[[Category: Hunter, W N.]] | [[Category: Hunter, W N.]] | ||
[[Category: Kemp, L E.]] | [[Category: Kemp, L E.]] | ||
[[Category: | [[Category: Isoprene biosynthesis]] | ||
[[Category: | [[Category: Isoprenoid]] | ||
[[Category: | [[Category: Lyase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:07:22 2008'' | |||
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Revision as of 18:07, 2 May 2008
STRUCTURE OF 2C-METHYL-D-ERYTHRITOL-2,4-CYCLODIPHOSPHATE SYNTHASE
OverviewOverview
The crystal structure of the zinc enzyme Escherichia coli 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase in complex with cytidine 5'-diphosphate and Mn(2+) has been determined to 1.8-A resolution. This enzyme is essential in E. coli and participates in the nonmevalonate pathway of isoprenoid biosynthesis, a critical pathway present in some bacterial and apicomplexans but distinct from that used by mammals. Our analysis reveals a homotrimer, built around a beta prism, carrying three active sites, each of which is formed in a cleft between pairs of subunits. Residues from two subunits recognize and bind the nucleotide in an active site that contains a Zn(2+) with tetrahedral coordination. A Mn(2+), with octahedral geometry, is positioned between the alpha and beta phosphates acting in concert with the Zn(2+) to align and polarize the substrate for catalysis. A high degree of sequence conservation for the enzymes from E. coli, Plasmodium falciparum, and Mycobacterium tuberculosis suggests similarities in secondary structure, subunit fold, quaternary structure, and active sites. Our model will therefore serve as a template to facilitate the structure-based design of potential antimicrobial agents targeting two of the most serious human diseases, tuberculosis and malaria.
About this StructureAbout this Structure
1GX1 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development., Kemp LE, Bond CS, Hunter WN, Proc Natl Acad Sci U S A. 2002 May 14;99(10):6591-6. Epub 2002 May 7. PMID:11997478 Page seeded by OCA on Fri May 2 18:07:22 2008