1oj4: Difference between revisions

Revision as of 15:18, 21 February 2008

TERNARY COMPLEX OF 4-DIPHOSPHOCYTIDYL-2-C-METHYL-D-ERYTHRITOL KINASE

OverviewOverview

4-Diphosphocytidyl-2C-methyl-d-erythritol kinase, an essential enzyme in the nonmevalonate pathway of isopentenyl diphosphate and dimethylallyl diphosphate biosynthesis, catalyzes the single ATP-dependent phosphorylation stage affording 4-diphosphocytidyl-2C-methyl-d-erythritol-2-phosphate. The 2-A resolution crystal structure of the Escherichia coli enzyme in a ternary complex with substrate and a nonhydrolyzable ATP analogue reveals the molecular determinants of specificity and catalysis. The enzyme subunit displays the alpha/beta fold characteristic of the galactose kinase/homoserine kinase/mevalonate kinase/phosphomevalonate kinase superfamily, arranged into cofactor and substrate-binding domains with the catalytic center positioned in a deep cleft between domains. Comparisons with related members of this superfamily indicate that the core regions of each domain are conserved, whereas there are significant differences in the substrate-binding pockets. The nonmevalonate pathway is essential in many microbial pathogens and distinct from the mevalonate pathway used by mammals. The high degree of sequence conservation of the enzyme across bacterial species suggests similarities in structure, specificity, and mechanism. Our model therefore provides an accurate template to facilitate the structure-based design of broad-spectrum antimicrobial agents.

About this StructureAbout this Structure

1OJ4 is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, with EC number 2.7.1.148 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Biosynthesis of isoprenoids: crystal structure of 4-diphosphocytidyl-2C-methyl-D-erythritol kinase., Miallau L, Alphey MS, Kemp LE, Leonard GA, McSweeney SM, Hecht S, Bacher A, Eisenreich W, Rohdich F, Hunter WN, Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9173-8. Epub 2003 Jul 23. PMID:12878729

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 ==Overview==
--Diphosphocytidyl-2C-methyl-d-erythritol kinase, an essential enzyme in, the nonmevalonate pathway of isopentenyl diphosphate and dimethylallyl, diphosphate biosynthesis, catalyzes the single ATP-dependent, phosphorylation stage affording, 4-diphosphocytidyl-2C-methyl-d-erythritol-2-phosphate. The 2-A resolution, crystal structure of the Escherichia coli enzyme in a ternary complex with, substrate and a nonhydrolyzable ATP analogue reveals the molecular, determinants of specificity and catalysis. The enzyme subunit displays the, alpha/beta fold characteristic of the galactose kinase/homoserine, kinase/mevalonate kinase/phosphomevalonate kinase superfamily, arranged, into cofactor and substrate-binding domains with the catalytic center, positioned in a deep cleft between domains. Comparisons with related, members of this superfamily indicate that the core regions of each domain, are conserved, whereas there are significant differences in the, substrate-binding pockets. The nonmevalonate pathway is essential in many, microbial pathogens and distinct from the mevalonate pathway used by, mammals. The high degree of sequence conservation of the enzyme across, bacterial species suggests similarities in structure, specificity, and, mechanism. Our model therefore provides an accurate template to facilitate, the structure-based design of broad-spectrum antimicrobial agents.
+-Diphosphocytidyl-2C-methyl-d-erythritol kinase, an essential enzyme in the nonmevalonate pathway of isopentenyl diphosphate and dimethylallyl diphosphate biosynthesis, catalyzes the single ATP-dependent phosphorylation stage affording 4-diphosphocytidyl-2C-methyl-d-erythritol-2-phosphate. The 2-A resolution crystal structure of the Escherichia coli enzyme in a ternary complex with substrate and a nonhydrolyzable ATP analogue reveals the molecular determinants of specificity and catalysis. The enzyme subunit displays the alpha/beta fold characteristic of the galactose kinase/homoserine kinase/mevalonate kinase/phosphomevalonate kinase superfamily, arranged into cofactor and substrate-binding domains with the catalytic center positioned in a deep cleft between domains. Comparisons with related members of this superfamily indicate that the core regions of each domain are conserved, whereas there are significant differences in the substrate-binding pockets. The nonmevalonate pathway is essential in many microbial pathogens and distinct from the mevalonate pathway used by mammals. The high degree of sequence conservation of the enzyme across bacterial species suggests similarities in structure, specificity, and mechanism. Our model therefore provides an accurate template to facilitate the structure-based design of broad-spectrum antimicrobial agents.
 ==About this Structure==
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 [[Category: Escherichia coli]]
 [[Category: Single protein]]
-[[Category: Alphey, M.S.]]
+[[Category: Alphey, M S.]]
-[[Category: Hunter, W.N.]]
+[[Category: Hunter, W N.]]
 [[Category: Miallau, L.]]
 [[Category: ANP]]
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 [[Category: kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:58:46 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:18:20 2008''