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
4.99.1.8
-
RECOMMENDED NAME
GeneOntology No.
heme ligase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 ferriprotoporphyrin IX = beta-hematin
show the reaction diagram
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
hemoglobin degradation
-
-
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.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
alpha-HDP
Q8IL04
-
heme detoxification protein
-
-
heme detoxification protein
Q8IL04
-
heme detoxification protein
Q8IL04
-
-
heme detoxification protein
-
-
heme-detoxification protein
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
hemozoin is the main protective mechanism against heme toxicity in malaria parasites
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ferriprotoporphyrin IX
beta-hematin
show the reaction diagram
-
-
-
-
?
ferriprotoporphyrin IX
beta-hematin
show the reaction diagram
-
-
beta-hematin is also called hemozoin
-
?
ferriprotoporphyrin IX
beta-hematin
show the reaction diagram
-
-
beta-hematin is also called hemozoin or Malaria pigment
-
?
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
-
-
?
ferriprotoporphyrin IX
beta-hematin
show the reaction diagram
-
HDP possesses 2.7 heme binding sites
-
-
?
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
-
-
?
heme
hemozoin
show the reaction diagram
Q8IL04
-
-
-
?
heme
hemozoin
show the reaction diagram
-
-
-
-
?
heme
hemozoin
show the reaction diagram
-
most efficient substrate
-
-
?
heme
hemozoin
show the reaction diagram
Q8IL04
-
-
-
?
oleoyl glycerol
?
show the reaction diagram
-
-
-
-
?
palmitoyl glycerol
?
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
-
?
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.3 - 5.2
-
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
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the parasite utilizes a circuitous outbound-inbound trafficking route by initially secreting HDP into the cytosol of infected red blood cells
-
Manually annotated by BRENDA team
-
digestive food vacuole
Manually annotated by BRENDA team
-
falcipain 2 coexists with heme detoxification protein and forms a hemozoin formation complex in the Plasmodium food vacuole
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 25000, SDS-PAGE
?
-
x * 23000, recombinant non-tagged enzyme, SDS-PAGE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
94
-
10 min, stable
694830
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HiTrap Q column chromatography and Sephadex G25 gel filtration
-
HiTrap Q column chromatography and Superdex 75 gel filtration
-
native enzyme, full-length recombinant enzyme and truncated enzymes
-
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
-
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)
-
expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H122A
-
the mutant shows less than half of the wild type activity
H172A
-
the mutant shows 44% of the wild type activity
H175A
-
the mutant shows less than half of the wild type activity
H192A
-
the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H197A
-
the mutant shows less than half of the wild type activity
H44A
-
the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H44A/H58A/H70A/H79A/H122A/H172A/H175A/H192A/H197A
-
the mutant shows less than half of the wild type activity
H58A
-
the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H70A
-
the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
H79A
-
the mutant shows decreased hemozoin formation activity compared to the wild type enzyme
additional information
-
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
LITERATURE
medicine
-
HDP is a conserved target for future antimalarial development
medicine
-
involvement of heme detoxification protein in the process of formation of hemozoin suggests that it could be a malaria drug target