1N4R

Protein Geranylgeranyltransferase type-I Complexed with a Geranylgeranylated KKKSKTKCVIL Peptide Product

Summary for 1N4R

• Entry DOI: 10.2210/pdb1n4r/pdb
• Related: 1D8D 1DCE 1FPP 1FT1 1KZO 1KZP 1N4P 1N4Q 1N4S 1QBQ
• Descriptor: 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, ... (9 entities in total)
• Functional Keywords: protein geranylgeranyltransferase type-i, ggtase, geranylgeranyl, protein prenylation, caax, lipid modification, rap2b, transferase
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 18
• Total formula weight: 531105.36

Authors

Taylor, J.S.,Reid, T.S.,Casey, P.J.,Beese, L.S. (deposition date: 2002-11-01, release date: 2003-11-18, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)