3p10 | pdb_00003p10

Crystal structure of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Burkholderia pseudomallei with cytidine and FOL694, 2-(thiophen-2-yl)phenyl methanol

spinqualitylabelsall models 3p10, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3p10 is a 3 chain structure with sequence from Burp1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, CTN, F69, K, ZN Related: 3f0d, 3jvh, 3ike, 3ieq, 3ikf, 3mbm, 3k14, 3ke1, 3p0z Gene: ispF, BURPS1710b_2511 (BURP1) Activity: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, with EC number 4.6.1.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ISPF_BURP1] Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP) (By similarity).[HAMAP-Rule:MF_00107] Publication Abstract from PubMed As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme. Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei.,Begley DW, Hartley RC, Davies DR, Edwards TE, Leonard JT, Abendroth J, Burris CA, Bhandari J, Myler PJ, Staker BL, Stewart LJ J Struct Funct Genomics. 2011 Jul;12(2):63-76. Epub 2011 Feb 26. PMID:21359640 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also MECDP synthase 3D structures

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