3Q8H
Crystal structure of 2c-methyl-d-erythritol 2,4-cyclodiphosphate synthase from burkholderia pseudomallei in complex with cytidine derivative EBSI01028
Summary for 3Q8H
| Entry DOI | 10.2210/pdb3q8h/pdb |
| Related | 3f0d 3ieq 3ike 3ikf 3jvh 3k14 3ke1 3mbm 3p0z |
| Descriptor | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, ZINC ION, 5'-deoxy-5'-[(imidazo[2,1-b][1,3]thiazol-5-ylcarbonyl)amino]cytidine, ... (6 entities in total) |
| Functional Keywords | seattle structural genomics center for infectious disease, ssgcid, ispf, mep pathway, lyase, metal-binding, isoprene biosynthesis |
| Biological source | Burkholderia pseudomallei (Pseudomonas pseudomallei) |
| Total number of polymer chains | 3 |
| Total formula weight | 59997.96 |
| Authors | Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2011-01-06, release date: 2011-01-19, Last modification date: 2023-09-13) |
| Primary citation | 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., 23:6860-6863, 2013 Cited by 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: 24157367DOI: 10.1016/j.bmcl.2013.09.101 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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