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Literature summary for 4.2.1.114 extracted from

  • Do, E.; Park, M.; Hu, G.; Caza, M.; Kronstad, J.W.; Jung, W.H.
    The lysine biosynthetic enzyme Lys4 influences iron metabolism, mitochondrial function and virulence in Cryptococcus neoformans (2016), Biochem. Biophys. Res. Commun., 477, 706-711 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 4.2.1.114

Application

Application Comment Organism
drug development the enzyme is a possible antifungal drug target Cryptococcus neoformans var. grubii serotype A

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of GFP-tagged enzyme targeted to mitochondria Cryptococcus neoformans var. grubii serotype A

Protein Variants

Protein Variants Comment Organism
additional information generation of a CNAG_02565 deletion mutant, the deletion impairs mitochondrial functions, phenotype, overview Cryptococcus neoformans var. grubii serotype A

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Cryptococcus neoformans var. grubii serotype A 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ required, in a Fe-S cluster Cryptococcus neoformans var. grubii serotype A

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(R)-2-hydroxybutane-1,2,4-tricarboxylate Cryptococcus neoformans var. grubii serotype A
-
 (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 ?
(R)-2-hydroxybutane-1,2,4-tricarboxylate Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487
-
 (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 ?
(R)-2-hydroxybutane-1,2,4-tricarboxylate + H2O Cryptococcus neoformans var. grubii serotype A
-
 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
(R)-2-hydroxybutane-1,2,4-tricarboxylate + H2O Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487
-
 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
(Z)-but-1-ene-1,2,4-tricarboxylate + H2O Cryptococcus neoformans var. grubii serotype A
-
 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
(Z)-but-1-ene-1,2,4-tricarboxylate + H2O Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487
-
 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?

Organism

Organism UniProt Comment Textmining
Cryptococcus neoformans var. grubii serotype A J9VIU5
-
-
Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487 J9VIU5
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(R)-2-hydroxybutane-1,2,4-tricarboxylate
-
 Cryptococcus neoformans var. grubii serotype A (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 ?
(R)-2-hydroxybutane-1,2,4-tricarboxylate
-
 Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487 (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 ?
(R)-2-hydroxybutane-1,2,4-tricarboxylate + H2O
-
 Cryptococcus neoformans var. grubii serotype A (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
(R)-2-hydroxybutane-1,2,4-tricarboxylate + H2O
-
 Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
(Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 Cryptococcus neoformans var. grubii serotype A (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
(Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 Cryptococcus neoformans var. grubii serotype A H99 / ATCC 208821 / CBS 10515 / FGSC 9487 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?

Synonyms

Synonyms Comment Organism
CNAG_02565
-
 Cryptococcus neoformans var. grubii serotype A
Homoaconitase
-
 Cryptococcus neoformans var. grubii serotype A
LYS4
-
 Cryptococcus neoformans var. grubii serotype A

Cofactor

Cofactor Comment Organism Structure
Fe-S cluster
-
 Cryptococcus neoformans var. grubii serotype A

Expression

Organism Comment Expression
Cryptococcus neoformans var. grubii serotype A the gene CNAG_02565 is significantly downregulated in the cfo1 mutant down

General Information

General Information Comment Organism
malfunction deletion of the CNAG_02565 gene results in lysine auxotrophy. The lys4 mutant shows increased sensitivity to oxidative stress, agents that challenge cell wall/membrane integrity, and azole antifungal drugs. The phenotype is due in part to impaired mitochondrial function as a result of LYS4 deletion, which disrupts iron homeostasis in the organelle. The lys4 mutant is attenuated virulence in a mouse inhalation model of cryptococcosis. Loss of the enzyme results in organelle dysfunction due to a potential impact on Fe-S levels Cryptococcus neoformans var. grubii serotype A
physiological function the enzyme expression is regulated by iron levels and by the iron-related transcription factors Hap3 and HapX. The enzyme is essential for lysine biosynthesis and is required for full virulence. The iron metabolism and homeostasis have a large influence on the virulence of Cryptococcus neoformans Cryptococcus neoformans var. grubii serotype A