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Literature summary extracted from

  • Mabanglo, M.F.; Hast, M.A.; Lubock, N.B.; Hellinga, H.W.; Beese, L.S.
    Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design (2014), Protein Sci., 23, 289-301.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.5.1.58 drug development the enzyme from Aspergillus fumigatus is a target for antifungal drug design Aspergillus fumigatus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.5.1.58 purified enzyme in complex with substrate farnesyl diphosphate, and inhibitors FPT-II-KCVVM, tipifarnib, andin ternary complex with farnesyl diphosphate and inhibitor ED5, X-ray diffraction structure determination and analysis at 1.45-1.90 A resolution, structure modelling Aspergillus fumigatus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.58 ED5 i.e. N-(N-tert-butoxycarbonylpiperidin-4-ylmethyl), N-(2-[((4-cyanophenyl)-3-methyl-3H-imidazol-4-ylmethyl)-amino]-ethyl) 2-methylbenzenesulfonamide, an ethylenediamine-scaffold inhibitor Aspergillus fumigatus
2.5.1.58 farnesyl diphosphate inhibitor II FPT-II Aspergillus fumigatus
2.5.1.58 additional information inhibitor structure-function analysis for antifungal drug design, comparisons of enzyme-inhibitor complex crystal structures from Aspergillus fumigatus with structures from Homo sapiens (PDB IDs 1KZO and 1TN6) and Cryptococcus neoformans (PDB ID 3Q75), Peptide-induced conformational changes, overview. Binding groove widening is consistent with variations in steady-state enzyme kinetics Aspergillus fumigatus
2.5.1.58 tipifarnib an ethylenediamine-scaffold inhibitor Aspergillus fumigatus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.5.1.58 additional information
-
 additional information steady-state enzyme kinetics Aspergillus fumigatus
2.5.1.58 0.00076
-
 (2E,6E)-farnesyl diphosphate pH 7.5, 25°C Aspergillus fumigatus
2.5.1.58 0.00131
-
 KGCVIM pH 7.5, 25°C Aspergillus fumigatus
2.5.1.58 0.00184
-
 KGCVVM pH 7.5, 25°C Aspergillus fumigatus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.5.1.58 Mg2+ required Aspergillus fumigatus
2.5.1.58 Zn2+ required Aspergillus fumigatus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine Aspergillus fumigatus
-
 S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.58 Aspergillus fumigatus
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.58 (2E,6E)-farnesyl diphosphate + KGCVIM
-
 Aspergillus fumigatus S-(2E,6E)-farnesyl-KGCVIM + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + KGCVVM
-
 Aspergillus fumigatus S-(2E,6E)-farnesyl-KGCVVM + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine
-
 Aspergillus fumigatus S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?
2.5.1.58 (2E,6E)-farnesyl diphosphate + [protein]-L-cysteine the reaction is catalyzed by protein farnesyltransferase on protein substrates bearing the C-terminal CaaX motif Aspergillus fumigatus S-(2E,6E)-farnesyl-[protein]-L-cysteine + diphosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.58 AfFTase
-
 Aspergillus fumigatus
2.5.1.58 FTase
-
 Aspergillus fumigatus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.5.1.58 25
-
 assay at Aspergillus fumigatus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.5.1.58 0.12
-
 (2E,6E)-farnesyl diphosphate pH 7.5, 25°C Aspergillus fumigatus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.5.1.58 7.5
-
 assay at Aspergillus fumigatus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.5.1.58 0.000275
-
 pH 7.5, 25°C Aspergillus fumigatus ED5
2.5.1.58 0.0024
-
 pH 7.5, 25°C Aspergillus fumigatus tipifarnib