2H6G

W102T Protein Farnesyltransferase Mutant Complexed with a Geranylgeranylated DDPTASACVLS Peptide Product at 1.85A Resolution

Summary for 2H6G

• Entry DOI: 10.2210/pdb2h6g/pdb
• Related: 1FPP 1JCQ 1KZP 1N4R 1TN8 2H6F 2H6H 2H6I
• Related PRD ID: PRD_900003
• Descriptor: Protein farnesyltransferase/geranylgeranyltransferase type I alpha subunit, Protein farnesyltransferase beta subunit, farnesylated peptide, ... (7 entities in total)
• Functional Keywords: ftase, farnesyltransferase, farnesyl transferase, prenyltransferase, caax, ras, lipid modification, prenylation, substrate selectivity, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 95362.48

Authors

Terry, K.L.,Beese, L.S. (deposition date: 2006-05-31, release date: 2006-08-29, Last modification date: 2024-10-16)

Primary citation

Terry, K.L.,Casey, P.J.,Beese, L.S.
Conversion of protein farnesyltransferase to a geranylgeranyltransferase.
Biochemistry, 45:9746-9755, 2006

PubMed Abstract: Posttranslational modifications are essential for the proper function of a number of proteins in the cell. One such modification, the covalent attachment of a single isoprenoid lipid (prenylation), is carried out by the CaaX prenyltransferases, protein farnesyltransferase (FTase) and protein geranylgeranyltransferase type-I (GGTase-I). Substrate proteins of these two enzymes are involved in a variety of cellular functions but are largely associated with signal transduction. These modified proteins include members of the Ras superfamily, heterotrimeric G-proteins, centromeric proteins, and a number of proteins involved in nuclear integrity. Although FTase and GGTase-I are highly homologous, they are quite selective for their substrates, particularly for their isoprenoid diphosphate substrates, FPP and GGPP, respectively. Here, we present both crystallographic and kinetic analyses of mutants designed to explore this isoprenoid specificity and demonstrate that this specificity is dependent upon two enzyme residues in the beta subunits of the enzymes, W102beta and Y365beta in FTase (T49beta and F324beta, respectively, in GGTase-I).

PubMed: 16893176
DOI: 10.1021/bi060295e

Experimental method

X-RAY DIFFRACTION (1.85 Å)