4rxe | pdb_00004rxe

T. Brucei Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-14

spinqualitylabelsall models 4rxe, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rxe is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3YQ, MG Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Farnesyl diphosphate synthase (FPPS) is an important drug target for bone resorption, cancer, and some infectious diseases. Here, we report five new structures including two having unique bound ligand geometries. The diamidine inhibitor 7 binds to human FPPS close to the homoallylic (S2) and allosteric (S3) sites and extends into a new site, here called S4. With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. We also report the structures of apo-FPPS from T. brucei, together with two more bisphosphonate-bound structures (2,9), for purposes of comparison. The diamidine structure is of particular interest because 7 could represent a new lead for lipophilic FPPS inhibitors, while 8 has low micromolar activity against T. brucei, the causative agent of human African trypanosomiasis. Farnesyl diphosphate synthase inhibitors with unique ligand-binding geometries.,Liu YL, Cao R, Wang Y, Oldfield E ACS Med Chem Lett. 2015 Jan 29;6(3):349-54. doi: 10.1021/ml500528x. eCollection, 2015 Mar 12. PMID:25815158 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA