1KZP

PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYLATED K-RAS4B PEPTIDE PRODUCT

1KZP の概要

• エントリーDOI: 10.2210/pdb1kzp/pdb
• 関連するPDBエントリー: 1D8D 1FT1 1FT2 1JCQ 1kzo 1kzr
• 分子名称: Protein Farnesyltransferase alpha subunit, Protein Farnesyltransferase beta subunit, Farnesylated K-Ras4B peptide product, ... (7 entities in total)
• 機能のキーワード: ftase, pft, pftase, ft, fpt, farnesyltransferase, farnesyl transferase, farnesyl protein transferase, caax, ras cancer, transferase-transferase substrate complex, transferase/transferase substrate
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 94511.03

構造登録者

Long, S.B.,Casey, P.J.,Beese, L.S. (登録日: 2002-02-07, 公開日: 2002-10-16, 最終更新日: 2024-11-13)

主引用文献

Long, S.B.,Casey, P.J.,Beese, L.S.
Reaction path of protein farnesyltransferase at atomic resolution
Nature, 419:645-650, 2002

PubMed Abstract: Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of human cancers, is essential for their transforming activity. FTase inhibitors are currently in clinical trials for the treatment of cancer. Here we present a complete series of structures representing the major steps along the reaction coordinate of this enzyme. From these observations can be deduced the determinants of substrate specificity and an unusual mechanism in which product release requires binding of substrate, analogous to classically processive enzymes. A structural model for the transition state consistent with previous mechanistic studies was also constructed. The processive nature of the reaction suggests the structural basis for the successive addition of two prenyl groups to Rab proteins by the homologous enzyme geranylgeranyltransferase type-II. Finally, known FTase inhibitors seem to differ in their mechanism of inhibiting the enzyme.

PubMed: 12374986
DOI: 10.1038/nature00986

実験手法

X-RAY DIFFRACTION (2.1 Å)