4RXA

Crystal structure of human farnesyl diphosphate synthase in complex with BPH-1358

4RXA の概要

• エントリーDOI: 10.2210/pdb4rxa/pdb
• 分子名称: Farnesyl pyrophosphate synthase, N,N'-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]biphenyl-4,4'-dicarboxamide, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: prenylation, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P14324
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40653.27

構造登録者

Liu, Y.-L.,Cao, R.,Wang, Y.,Oldfield, E. (登録日: 2014-12-09, 公開日: 2015-04-15, 最終更新日: 2024-02-28)

主引用文献

Liu, Y.L.,Cao, R.,Wang, Y.,Oldfield, E.
Farnesyl diphosphate synthase inhibitors with unique ligand-binding geometries.
ACS Med Chem Lett, 6:349-354, 2015

PubMed Abstract: 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.

PubMed: 25815158
DOI: 10.1021/ml500528x

実験手法

X-RAY DIFFRACTION (2.2 Å)