3DPY

Protein farnesyltransferase complexed with FPP and caged TKCVIM substrate

3DPY の概要

• エントリーDOI: 10.2210/pdb3dpy/pdb
• 関連するPDBエントリー: 1D8D
• 分子名称: Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha, Protein farnesyltransferase subunit beta, caged substrate, ... (7 entities in total)
• 機能のキーワード: farnesyltransferase, ftase, pft, geranylgeranyltransferase, prenylation, protein prenylation, protein prenyltransferase, prenyltransferase, fpp, transferase, metal-binding, phosphoprotein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 94023.14

構造登録者

Hast, M.A.,Beese, L.S. (登録日: 2008-07-09, 公開日: 2008-09-30, 最終更新日: 2024-02-21)

主引用文献

DeGraw, A.J.,Hast, M.A.,Xu, J.,Mullen, D.,Beese, L.S.,Barany, G.,Distefano, M.D.
Caged protein prenyltransferase substrates: tools for understanding protein prenylation.
Chem.Biol.Drug Des., 72:171-181, 2008

PubMed Abstract: Originally designed to block the prenylation of oncogenic Ras, inhibitors of protein farnesyltransferase currently in preclinical and clinical trials are showing efficacy in cancers with normal Ras. Blocking protein prenylation has also shown promise in the treatment of malaria, Chagas disease and progeria syndrome. A better understanding of the mechanism, targets and in vivo consequences of protein prenylation are needed to elucidate the mode of action of current PFTase (Protein Farnesyltransferase) inhibitors and to create more potent and selective compounds. Caged enzyme substrates are useful tools for understanding enzyme mechanism and biological function. Reported here is the synthesis and characterization of caged substrates of PFTase. The caged isoprenoid diphosphates are poor substrates prior to photolysis. The caged CAAX peptide is a true catalytically caged substrate of PFTase in that it is to not a substrate, yet is able to bind to the enzyme as established by inhibition studies and X-ray crystallography. Irradiation of the caged molecules with 350 nm light readily releases their cognate substrate and their photolysis products are benign. These properties highlight the utility of those analogs towards a variety of in vitro and in vivo applications.

PubMed: 18844669
DOI: 10.1111/j.1747-0285.2008.00698.x

実験手法

X-RAY DIFFRACTION (2.7 Å)