Information on EC 4.99.1.8 - heme ligase

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The expected taxonomic range for this enzyme is: Plasmodium

EC NUMBER
COMMENTARY hide
4.99.1.8
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RECOMMENDED NAME
GeneOntology No.
heme ligase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 ferriprotoporphyrin IX = beta-hematin
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
hemoglobin degradation
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SYSTEMATIC NAME
IUBMB Comments
Fe3+:ferriprotoporphyrin IX ligase (beta-hematin-forming)
This heme detoxifying enzyme is found in Plasmodium parasites and converts toxic heme to crystalline hemozoin. These organisms lack the mammalian heme oxygenase for elimination of heme.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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hemozoin is the main protective mechanism against heme toxicity in malaria parasites
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ferriprotoporphyrin IX
beta-hematin
show the reaction diagram
heme
hemozoin
show the reaction diagram
oleoyl glycerol
?
show the reaction diagram
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-
-
-
?
palmitoyl glycerol
?
show the reaction diagram
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?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ferriprotoporphyrin IX
beta-hematin
show the reaction diagram
-
hemozoin consists of an unusual polymer of hemes linked between the central ferric ion of one heme and a carboxylate side-group oxygen of another. The hemes are sequestered via this linkage into an insoluble product, providing a unique way for the malaria parasite to avoid the toxicity associated with soluble heme
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?
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.3 - 5.2
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pH 3.3-4.4: optimum, pH 5.2: about 75% of maximal activity, no activity above pH 5.6
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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the parasite utilizes a circuitous outbound-inbound trafficking route by initially secreting HDP into the cytosol of infected red blood cells
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Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
94
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10 min, stable
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HiTrap Q column chromatography and Sephadex G25 gel filtration
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HiTrap Q column chromatography and Superdex 75 gel filtration
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native enzyme, full-length recombinant enzyme and truncated enzymes
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recombinant enzyme
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
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expression in Escherichia coli
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expression of full length enzyme in Escherichia coli, expression of two truncated enzyme proteins (HDP3 encoded by amino acids 88-205 of the full-length protein, representing the fasciclin domain and HDP2 encoded by amino acids 1–87 and lacking the fasciclin domain)
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H122A
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the mutant shows less than half of the wild type activity
H172A
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the mutant shows 44% of the wild type activity
H175A
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the mutant shows less than half of the wild type activity
H192A
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the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H197A
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the mutant shows less than half of the wild type activity
H44A
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the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H44A/H58A/H70A/H79A/H122A/H172A/H175A/H192A/H197A
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the mutant shows less than half of the wild type activity
H58A
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the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H70A
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the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H79A
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the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
additional information
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the truncated enzyme proteins HDP3 (encoded by amino acids 88-205 of the full-length protein, representing the fasciclin domain) and HDP2 (encoded by amino acids 1–87 and lacking the fasciclin domain) are unable to produce hemozoin. The full-length enzyme is required for heme binding and hemozoin production activities of the protein
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine