Literature summary for 2.5.1.58 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.

Application

Application	Comment	Organism
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)

Cloned (Comment)	Organism
-	Cryptococcus neoformans

Crystallization (Commentary)

Crystallization (Comment)	Organism
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

Crystallization (Comment)

Organism

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

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

Organism

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

Purification (Commentary)

Purification (Comment)	Organism
recombinant protein	Cryptococcus neoformans

General Information

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