Literature summary for 1.14.14.154 extracted from

Sheng, C.; Miao, Z.; Ji, H.; Yao, J.; Wang, W.; Che, X.; Dong, G.; Lue, J.; Guo, W.; Zhang, W.
Three-dimensional model of lanosterol 14 alpha-demethylase from Cryptococcus neoformans: active-site characterization and insights into azole binding (2009), Antimicrob. Agents Chemother., 53, 3487-3495.

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Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	active site with four functional regions	Cryptococcus neoformans

Application

Application	Comment	Organism
drug development	structural model of CYP51 can be used in azole optimization, virtual screening, or de novo inhibitor design for the discovery of new antifungal agents	Cryptococcus neoformans

Protein Variants

Protein Variants	Comment	Organism
G484S	azole resistance	Cryptococcus neoformans

Inhibitors

Inhibitors	Comment	Organism	Structure
albaconazole	lower interaction energies with CYP51 than those of voriconazole	Cryptococcus neoformans
fluconazole	is bound to the active site of CYP51 through the formation of a coordination bond with the iron of the heme group (the P1 subsite). The difluorophenyl group of fluconazole points toward substrate access channel 1 (the BC loop) and forms a hydrophobic interaction with Met153 and the alkyl group of Lys157 (the P3 subsite). Another triazolyl ring of fluconazole attached to C-3 has a preferable orientation toward substrate access channel 2 (the FG loop) and forms indirect nonbonding interactions with the surrounding residues, lined with Leu134, Phe240, Met316, Ile386, and Ile529 (the P4 subsite). The hydroxyl group attached to C-2 is important for antifungal activity, but no interaction between this hydroxyl group and the active site of CYP51	Cryptococcus neoformans
itraconazole	lowest interaction energies with CYP51	Cryptococcus neoformans
posaconazole	lowest interaction energies with CYP51	Cryptococcus neoformans
ravuconazole	thiazole ring interacts with the side chain of Tyr131, Leu134, and Ile389. Besides the hydrophobic interaction with Phe240, Met528, and Ile529, the 4-cyano-phenyl group of ravuconazole can also form a pi-pi stacking interaction with His133	Cryptococcus neoformans
voriconazole	shows higher affinity with CYP51 than fluconazole	Cryptococcus neoformans

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Iron	-	Cryptococcus neoformans

Organism

Organism	UniProt	Comment	Textmining
Cryptococcus neoformans	Q870D1	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
24(28)-methylene-24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2	-	Cryptococcus neoformans	4,4-dimethyl-ergosta-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O	-	?

Synonyms

Synonyms	Comment	Organism
CYP51	-	Cryptococcus neoformans

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Release 2023.1 (January 2023)