3KE1

Crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Burkholderia pseudomallei in complex with a fragment-nucleoside fusion D000161829

3KE1 の概要

• エントリーDOI: 10.2210/pdb3ke1/pdb
• 関連するPDBエントリー: 3ieq 3ike 3ikf 3jvh 3k14 3k2x
• 分子名称: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, ZINC ION, 5'-deoxy-5'-[(pyridin-4-ylcarbonyl)amino]cytidine, ... (5 entities in total)
• 機能のキーワード: niaid, ssgcid, seattle structural genomics center for infectious disease, fragment crystallography, fbdd, fragment-based drug-design, nucleoside analog, d000161829, isoprene biosynthesis, lyase, metal-binding
• 由来する生物種: Burkholderia pseudomallei (Pseudomonas pseudomallei)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 59738.63

構造登録者

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2009-10-23, 公開日: 2009-11-10, 最終更新日: 2023-09-06)

主引用文献

Zhang, Z.,Jakkaraju, S.,Blain, J.,Gogol, K.,Zhao, L.,Hartley, R.C.,Karlsson, C.A.,Staker, B.L.,Edwards, T.E.,Stewart, L.J.,Myler, P.J.,Clare, M.,Begley, D.W.,Horn, J.R.,Hagen, T.J.
Cytidine derivatives as IspF inhibitors of Burkolderia pseudomallei.
Bioorg.Med.Chem.Lett., 8:e53851-e53851, 2013

PubMed Abstract: Published biological data suggest that the methyl erythritol phosphate (MEP) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. One highly conserved enzyme in the MEP pathway is 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF). Fragment-bound complexes of IspF from Burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fragment binders. Testing by surface plasmon resonance (SPR) found one molecule in the series to possess binding affinity equal to that of cytidine diphosphate, despite lacking any metal-coordinating phosphate groups. Close inspection of the SPR data suggest different binding stoichiometries between IspF and test compounds. Crystallographic analysis shows important variations between the binding mode of one synthesized compound and the pose of the bound fragment from which it was designed. The binding modes of these molecules add to our structural knowledge base for IspF and suggest future refinements in this compound series.

PubMed: 24157367
DOI: 10.1016/j.bmcl.2013.09.101

実験手法

X-RAY DIFFRACTION (2.05 Å)