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Literature summary 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

Application

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

Cloned(Commentary)

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

Protein Variants

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

Localization

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

Metals/Ions

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.2.1.114 (R)-2-hydroxybutane-1,2,4-tricarboxylate Cryptococcus neoformans var. grubii serotype A
-
 (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 ?
4.2.1.114 (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
-
 ?
4.2.1.114 (R)-2-hydroxybutane-1,2,4-tricarboxylate + H2O Cryptococcus neoformans var. grubii serotype A
-
 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
4.2.1.114 (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
-
 ?
4.2.1.114 (Z)-but-1-ene-1,2,4-tricarboxylate + H2O Cryptococcus neoformans var. grubii serotype A
-
 (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
4.2.1.114 (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

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.2.1.114 (R)-2-hydroxybutane-1,2,4-tricarboxylate
-
 Cryptococcus neoformans var. grubii serotype A (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 ?
4.2.1.114 (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
-
 ?
4.2.1.114 (R)-2-hydroxybutane-1,2,4-tricarboxylate + H2O
-
 Cryptococcus neoformans var. grubii serotype A (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
4.2.1.114 (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
-
 ?
4.2.1.114 (Z)-but-1-ene-1,2,4-tricarboxylate + H2O
-
 Cryptococcus neoformans var. grubii serotype A (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
 ?
4.2.1.114 (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

EC Number Synonyms Comment Organism
4.2.1.36 LYS4
-
 Cryptococcus neoformans var. grubii
4.2.1.114 CNAG_02565
-
 Cryptococcus neoformans var. grubii serotype A
4.2.1.114 Homoaconitase
-
 Cryptococcus neoformans var. grubii serotype A
4.2.1.114 LYS4
-
 Cryptococcus neoformans var. grubii serotype A

Cofactor

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

Expression

EC Number Organism Comment Expression
4.2.1.36 Cryptococcus neoformans var. grubii transcription factors HAP3 or HAPX negatively regulate expression of the gene, but only in iron-depleted conditions. The transcription factors do not influence LYS4 transcript levels upon iron repletion down
4.2.1.36 Cryptococcus neoformans var. grubii no LYS4 transcripts are observed in cells grown in low-iron medium, whereas abundant transcripts are observed in the cells grown in the high-iron medium. These results confirm the regulation of LYS4 by iron availability and indicate that the LYS4 gene is mainly transcribed when sufficient iron is present in the environment. Iron availability influences both transcript and protein levels for Lys4 up
4.2.1.114 Cryptococcus neoformans var. grubii serotype A the gene CNAG_02565 is significantly downregulated in the cfo1 mutant down

General Information

EC Number General Information Comment Organism
4.2.1.36 malfunction deletion of the LYS4 gene results in lysine auxotrophy. The mutant shows increased sensitivity to oxidative stress, agents that challenge cell wall/membrane integrity, and azole antifungal drugs Cryptococcus neoformans var. grubii
4.2.1.36 metabolism the enzyme is involved in the lysine biosynthetic pathway Cryptococcus neoformans var. grubii
4.2.1.36 physiological function Lys4 plays an important role in mitochondrial iron metabolism, and is required for proper mitochondrial function in Cryptococcus neoformans. LYS4 is required for full virulence in Cryptococcus neoformans Cryptococcus neoformans var. grubii
4.2.1.114 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
4.2.1.114 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