1t0a

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spinqualitylabelsall models 1t0a, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of 2C-Methyl-D-Erythritol-2,4-cyclodiphosphate Synthase from Shewanella Oneidensis

Overview

Isopentenyl pyrophosphate (IPP) is a universal building block for the, ubiquitous isoprenoids that are essential to all organisms. The enzymes of, the non-mevalonate pathway for IPP synthesis, which is unique to many, pathogenic bacteria, have recently been explored as targets for antibiotic, development. Several crystal structures of, 2C-methyl-D-erythritol-2,4-cyclophosphate (MECDP) synthase, the fifth of, seven enzymes involved in the non-mevalonate pathway for synthesis of IPP, have been reported; however, the composition of metal ions in the active, site and the presence of a hydrophobic cavity along the, non-crystallographic threefold symmetry axis has varied between the, reported structures. Here, the structure of MEDCP from Shewanella, oneidensis MR1 (SO3437) was determined to 1.6 A resolution in the absence, of substrate. The presence of a zinc ion in the active-site cleft, tetrahedrally coordinated by two histidine side chains, an aspartic acid, side chain and an ambiguous fourth ligand, was confirmed by zinc anomalous, diffraction. Based on analysis of anomalous diffraction data and typical, metal-to-ligand bond lengths, it was concluded that an octahedral sodium, ion was 3.94 A from the zinc ion. A hydrophobic cavity was observed along, the threefold non-crystallographic symmetry axis, filled by a well defined, non-protein electron density that could be modeled as farnesyl, pyrophosphate (FPP), a downstream product of IPP, suggesting a possible, feedback mechanism for enzyme regulation. The high-resolution data, clarified the FPP-binding mode compared with previously reported, structures. Multiple sequence alignment indicated that the residues, critical to the formation of the hydrophobic cavity and for coordinating, the pyrophosphate group of FPP are present in the majority of MEDCP, synthase enzymes, supporting the idea of a specialized biological function, related to FPP binding in a subfamily of MEDCP synthase homologs.

About this Structure

1T0A is a Single protein structure of sequence from Bacteria with ZN, CO and FPP as ligands. Active as 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, with EC number 4.6.1.12 Full crystallographic information is available from OCA.

Reference

Structure of 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase from Shewanella oneidensis at 1.6 A: identification of farnesyl pyrophosphate trapped in a hydrophobic cavity., Ni S, Robinson H, Marsing GC, Bussiere DE, Kennedy MA, Acta Crystallogr D Biol Crystallogr. 2004 Nov;60(Pt 11):1949-57. Epub 2004, Oct 20. PMID:15502301

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