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Literature summary extracted from

  • Hast, M.A.; Nichols, C.B.; Armstrong, S.M.; Kelly, S.M.; Hellinga, H.W.; Alspaugh, J.A.; Beese, L.S.
    Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens (2011), J. Biol. Chem., 286, 35149-35162.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.5.1.58 medicine 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 Cryptococcus neoformans

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.5.1.58
-
 Cryptococcus neoformans

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
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 Cryptococcus neoformans

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.58 manumycin A notable growth inhibition, application disrupts Ras1 localization in vivo Cryptococcus neoformans
2.5.1.58 tipifarnib notable growth inhibition Cryptococcus neoformans

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.58 Cryptococcus neoformans
-
 clinical isolate
-
2.5.1.58 Cryptococcus neoformans B-3501A
-
 clinical isolate
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.5.1.58 recombinant protein Cryptococcus neoformans

General Information

EC Number General Information Comment Organism
2.5.1.58 physiological function ras1 deletion phenotype can be mimicked chemically by inhibition of farnesyl transferase in the wild-type strain Cryptococcus neoformans