1N4P

Protein Geranylgeranyltransferase type-I Complexed with Geranylgeranyl Diphosphate

1N4P の概要

• エントリーDOI: 10.2210/pdb1n4p/pdb
• 関連するPDBエントリー: 1D8D 1DCE 1FPP 1FT1 1KZO 1KZP 1N4Q 1N4R 1N4S 1QBQ
• 分子名称: Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha, Geranylgeranyl transferase type-1 subunit beta, Fusion protein consisting of transforming protein p21b and Ras related protein Rap-2b, ... (8 entities in total)
• 機能のキーワード: protein geranylgeranyltransferase type-i, ggtase, geranylgeranyl, protein prenylation, caax, lipid modification, rap2b, transferase
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 525910.45

構造登録者

Taylor, J.S.,Reid, T.S.,Casey, P.J.,Beese, L.S. (登録日: 2002-11-01, 公開日: 2003-11-18, 最終更新日: 2024-02-14)

主引用文献

Taylor, J.S.,Reid, T.S.,Terry, K.L.,Casey, P.J.,Beese, L.S.
Structure of mammalian protein geranylgeranyltransferase type-I
EMBO J., 22:5963-5974, 2003

PubMed Abstract: Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first structural information for mammalian GGTase-I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15-C prenyl substrate) into GGTase-I (20-C prenyl substrate) with a single point mutation. GGTase-I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15-C FPP to displace the 20-C prenyl-peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs.

PubMed: 14609943
DOI: 10.1093/emboj/cdg571

実験手法

X-RAY DIFFRACTION (2.65 Å)