1RTR

Crystal Structure of S. Aureus Farnesyl Pyrophosphate Synthase

1RTR の概要

• エントリーDOI: 10.2210/pdb1rtr/pdb
• 関連するPDBエントリー: 1RQI 1RQJ
• 分子名称: geranyltranstransferase (2 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67722.70

構造登録者

Hosfield, D.J.,Zhang, Y.,Dougan, D.R.,Brooun, A.,Tari, L.W.,Swanson, R.V.,Finn, J. (登録日: 2003-12-10, 公開日: 2004-03-02, 最終更新日: 2024-02-14)

主引用文献

Hosfield, D.J.,Zhang, Y.,Dougan, D.R.,Brooun, A.,Tari, L.W.,Swanson, R.V.,Finn, J.
Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis
J.Mol.Biol., 279:8526-8529, 2004

PubMed Abstract: Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate through successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. The structures reveal how enzyme conformational changes organize conserved active site residues to exploit metal-induced ionization and substrate positioning for catalysis. The structures further demonstrate how nitrogen-containing bisphosphonates mimic a carbocation intermediate to inhibit the enzyme. Together, these FPPS complexes provide a structural template for the design of novel inhibitors that may prove useful for the treatment of osteoporosis and other clinical indications including cancer.

PubMed: 14672944
DOI: 10.1074/jbc.C300511200

実験手法

X-RAY DIFFRACTION (2.5 Å)