EC Number   |
|---|
   2.5.1.58 | - |
| 2.5.1.58 | a new crystalline form of enzyme for the mutant truncated 10 residues at the C-terminus |
| 2.5.1.58 | analysis of reaction mechanism using catalytically active crystals and comparison with the human enzyme. In the CAAX binding site, a single residue substitution at the a2 site from tyrosine to asparagine results in a deeper cavity in this region compared with the human enzyme. The prenylated product exit groove is wider in the Cryptococcus neoformans enzyme relative to human enzyme and varies in amino acid composition. A substrate-induced conformational change observed for the 4alpha-5alpha loop of results in a molecular surface in the active site with two distinct states that can be individually exploited for inhibitor design |
| 2.5.1.58 | at 2.25 Angstrom, zinc occurs at a junction between a hydrophilic surface groove near the subunit interface: peptide binding site, and a deep lipophilic cleft in the beta subunit lined with aromatic residues: farnesyl diphosphate binding site |
| 2.5.1.58 | complex of enzyme with (E,E)-[alpha,beta(n)-32P]-8-O-(3-benzoylbenzyl)-3,7-dimethyl-2,6-octadiene 1-diphosphate and of the enzyme with geranylgeranyl diphosphate |
| 2.5.1.58 | crystal structure of FTase complexed with FPP and L-778,123 |
| 2.5.1.58 | farnesyl diphosphate and peptide substrate can be accommodated in the hydrophobic active-site barrel, with the sole charged residue inside the barrel, Arg202 of the beta-subunit, forming a salt bridge with the negatively charged carboxy terminus of peptide substrate |
| 2.5.1.58 | FTase in ternary complexes with an FPP analog and peptides derived from the cognate substrates H-Ras (GCVLS) and Rap2a (DDPTA-SACNIQ), the cross-reactive substrate TC21 (KKSKTKCVIF), and the non-substrate Rap2b (TKCVIL). Structures of GGTase-I in ternary complexes with a GGPP analog (3'azaGGPP) and peptides derived from the cognate substrates Cdc42 splice isoform 2 (RRCVLL Ca1a2X motif) and the heterotrimeric G protein g2 subunit (FREKKFFCAIL), and the cross-reactive substrates RhoB (GCINCCKVL), K-Ras4B (KKKSKTKCVIM) and TC21 |
| 2.5.1.58 | molecular docking of inhibitors |
| 2.5.1.58 | molecular dynamics simulations to study enzyme flexibility in the 4 key intermediate states formed during the FTase catalytic mechanisms, ie. FTase resting state, binary complex FTase-FPP, ternary complex FTase-FPP-peptide, and product complex FTase-product. Relatively small-scale events such as substrate binding or product formation cause minor changes at the neighboring residues and corresponding helices, but ultimately induce much more dramatic effects on the more external regions of the enzyme |
