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Information on EC 4.1.3.16 - 4-Hydroxy-2-oxoglutarate aldolase and Organism(s) Homo sapiens and UniProt Accession Q86XE5
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4.1.3.16 4-Hydroxy-2-oxoglutarate aldolaseIUBMB Comments
The enzymes from rat liver and bovine liver act on both enantiomers of 4-hydroxy-2-oxoglutarate. cf. EC 4.1.3.42, (4S)-4-hydroxy-2-oxoglutarate aldolase.
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Word Map
- 4.1.3.16
- hyperoxalurias
- oxalate
-
stone
- ph2
- grhpr
- hydroxyproline
- urolithiasis
- 2-keto-3-deoxy-6-phosphogluconate
-
nephrocalcinosis
-
alanine-glyoxylate
-
nephrolithiasis
- synthesis
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
hoga1, 4-hydroxy-2-oxoglutarate aldolase, 2-keto-4-hydroxyglutarate aldolase, 2-oxo-4-hydroxyglutarate aldolase, dhdpsl, 4-hydroxy-2-ketoglutarate aldolase, entner-doudoroff aldolase, dihydrodipicolinate synthase-like enzyme, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-keto-4-hydroxybutyrate aldolase
-
-
-
-
2-keto-4-hydroxyglutarate aldolase
-
-
-
-
2-keto-4-hydroxyglutaric aldolase
-
-
-
-
2-oxo-4-hydroxyglutarate aldolase
-
-
-
-
2-oxo-4-hydroxyglutaric aldolase
-
-
-
-
4-hydroxy-2-ketoglutarate aldolase
-
-
-
-
4-hydroxy-2-ketoglutaric aldolase
-
-
-
-
aldolase, 4-hydroxy-2-oxoglutarate
-
-
-
-
DL-4-Hydroxy-2-ketoglutarate aldolase
-
-
-
-
hydroxyketoglutarate aldolase
-
-
-
-
Hydroxyketoglutaric aldolase
-
-
-
-
KHG-aldolase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
condensation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
4-hydroxy-2-oxoglutarate glyoxylate-lyase (pyruvate-forming)
The enzymes from rat liver and bovine liver act on both enantiomers of 4-hydroxy-2-oxoglutarate. cf. EC 4.1.3.42, (4S)-4-hydroxy-2-oxoglutarate aldolase.
CAS REGISTRY NUMBER
COMMENTARY
9030-81-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
enzyme performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases
-
-
?
additional information
?
-
-
enzyme performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
malfunction
-
primary hyperoxaluria type 3 is due to mutations in the 4-hydroxy-2-oxoglutarate aldolase gene
malfunction
enzyme mutations ultimately lead to oxalate accumulation and stone formation in primary hyperoxaluria type 3
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HOGA1_HUMAN
327
0
35249
Swiss-Prot
Mitochondrion (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35249
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 1.97 A resolution, crystal structure of enzyme bound to pyruvate. Modeling of the 4-hydroxy-2-oxoglutarate-Schiff base intermediate and kinetic analyses of site-directed mutants support the importance of Lys196 as the nucleophile, Tyr168 and Ser77 as components of a proton relay, and Asn78 and Ser198 as unique residues that facilitate substrate binding
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C257G
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
DeltaE315
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
G287V
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
P190L
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R255X
a truncation of 71 residues from the C-terminus associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R303C
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R70P
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
R97C
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
T280I
natural mutation associated with Primary Hyperoxaluria type 3. Mutant is quite unstable, has a tendency to aggregate, and retains no measurable activity
Y39X/R70X
naturally occuring mutations in a patient with type 3 atypical primary hyperoxaluria
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
genotyping in 28 patients with type 3 atypical primary hyperoxaluria, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase are associated with an excessive production of oxalate in Primary Hyperoxaluria type 3, PH3. Analysis of nine PH3 human variants reveals that all nine PH3 variants are quite unstable, have a tendency to aggregate, and retain no measurable activity. A buildup of 4-hydroxy-2-oxoglutarate takes place in the urine, sera and liver samples from PH3 patients. One hypothetical component of the molecular basis for the excessive oxalate production in PH3 appears to be the inhibition of glyoxylate reductase by 4-hydroxy-2-oxoglutarate, resulting in a phenotype similar to Primary Hyperoxaluria type 2
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Belostotsky, R.; Seboun, E.; Idelson, G.H.; Milliner, D.S.; Becker-Cohen, R.; Rinat, C.; Monico, C.G.; Feinstein, S.; Ben-Shalom, E.; Magen, D.; Weissman, I.; Charon, C.; Frishberg, Y.
Mutations in DHDPSL are responsible for primary hyperoxaluria type III
Am. J. Hum. Genet.
87
392-399
2010
Homo sapiens (Q86XE5), Homo sapiens
Riedel, T.J.; Knight, J.; Murray, M.S.; Milliner, D.S.; Holmes, R.P.; Lowther, W.T.
4-Hydroxy-2-oxoglutarate aldolase inactivity in primary hyperoxaluria type 3 and glyoxylate reductase inhibition
Biochim. Biophys. Acta
1822
1544-1552
2012
Homo sapiens (Q86XE5), Homo sapiens
Riedel, T.J.; Johnson, L.C.; Knight, J.; Hantgan, R.R.; Holmes, R.P.; Lowther, W.T.
Structural and biochemical studies of human 4-hydroxy-2-oxoglutarate aldolase: implications for hydroxyproline metabolism in primary hyperoxaluria
PLoS ONE
6
e26021
2011
Homo sapiens (Q86XE5), Homo sapiens
Williams, E.L.; Bockenhauer, D.; vant Hoff, W.G.; Johri, N.; Laing, C.; Sinha, M.D.; Unwin, R.; Viljoen, A.; Rumsby, G.
The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary hyperoxaluria type 3
Nephrol. Dial. Transplant.
27
3191-3195
2012
Homo sapiens (Q86XE5), Homo sapiens
MacDonald, J.R.; Huang, A.D.; Loomes, K.M.
Cellular degradation of 4-hydroxy-2-oxoglutarate aldolase leads to absolute deficiency in primary hyperoxaluria type 3
FEBS Lett.
590
1467-1476
2016
Homo sapiens (Q86XE5)
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