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Literature summary for 1.13.11.71 extracted from

  • Li, B.; Vachali, P.P.; Gorusupudi, A.; Shen, Z.; Sharifzadeh, H.; Besch, B.M.; Nelson, K.; Horvath, M.M.; Frederick, J.M.; Baehr, W.; Bernstein, P.S.
    Inactivity of human beta,beta-carotene-9',10'-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment (2014), Proc. Natl. Acad. Sci. USA, 111, 10173-10178 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene bco2, recombinant expression in Escherichia coli Homo sapiens
gene bco2, recombinant expression in Escherichia coli Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information GKAA represents an extension of human BCO2 exon 3 caused by use of an alternate donor splice site. Deletion of GKAA between P125 and M127 and replacement of A126 by T are expected to induce a substantial change in structure in this area, but no significant difference is found at their enzymatic cleavage domains, as all four key histidine residues are conserved. Simple deletion of GKAA cannot convert human BCO2 into an active carotenoid cleavage enzyme. Also replacing the N-terminal 197 amino acids of human BCO2a with the N-terminal 150 amino acids of mouse BCO2 or substitution of a wide range of amino acid residues of human BCO2 with the corresponding residues of mouse BCO2 cannot restore human BCO2's cleavage activity. Combined deletion of GKAA from human BCO2 with several key amino acid substitutions selected from the mouse BCO2 sequence still cannot rescue human BCO2's function Homo sapiens
additional information insertion of GKAA into mouse BCO2, in analogy to the inactive human enzyme, inactivates the mutant mouse enzyme, demonstrating that the GKAA insertion alone is sufficient to inactivate mouse BCO2 Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
all-trans-beta-carotene + O2 Homo sapiens
-
all-trans-10'-apo-beta-carotenal + beta-ionone
-
?
all-trans-beta-carotene + O2 Mus musculus
-
all-trans-10'-apo-beta-carotenal + beta-ionone
-
?
all-trans-beta-carotene + O2 Mus musculus C57/BL6
-
all-trans-10'-apo-beta-carotenal + beta-ionone
-
?
lutein + O2 Mus musculus
-
?
-
?
lutein + O2 Mus musculus C57/BL6
-
?
-
?
meso-zeaxanthin + O2 Mus musculus
-
?
-
?
meso-zeaxanthin + O2 Mus musculus C57/BL6
-
?
-
?
additional information Homo sapiens inactivity of BCO2 with xanthophylls such as zeaxanthin ?
-
?
zeaxanthin + O2 Mus musculus
-
3-hydroxy-beta-apo-10'-carotenal + 3-hydroxy-beta-ionone
-
?
zeaxanthin + O2 Mus musculus C57/BL6
-
3-hydroxy-beta-apo-10'-carotenal + 3-hydroxy-beta-ionone
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9BYV7
-
-
Mus musculus Q99NF1
-
-
Mus musculus C57/BL6 Q99NF1
-
-

Source Tissue

Source Tissue Comment Organism Textmining
additional information human retinal BCO2 is an inactive enzyme Homo sapiens
-
retina macular pigment Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
all-trans-beta-carotene + O2
-
Homo sapiens all-trans-10'-apo-beta-carotenal + beta-ionone
-
?
all-trans-beta-carotene + O2
-
Mus musculus all-trans-10'-apo-beta-carotenal + beta-ionone
-
?
all-trans-beta-carotene + O2
-
Mus musculus C57/BL6 all-trans-10'-apo-beta-carotenal + beta-ionone
-
?
lutein + O2
-
Mus musculus ?
-
?
lutein + O2
-
Mus musculus C57/BL6 ?
-
?
meso-zeaxanthin + O2
-
Mus musculus ?
-
?
meso-zeaxanthin + O2
-
Mus musculus C57/BL6 ?
-
?
additional information inactivity of BCO2 with xanthophylls such as zeaxanthin Homo sapiens ?
-
?
additional information human BCO2 isoform a (human BCO2a) fails to cleave zeaxanthin, retaining the yellow color Homo sapiens ?
-
?
zeaxanthin + O2
-
Mus musculus 3-hydroxy-beta-apo-10'-carotenal + 3-hydroxy-beta-ionone
-
?
zeaxanthin + O2
-
Mus musculus C57/BL6 3-hydroxy-beta-apo-10'-carotenal + 3-hydroxy-beta-ionone
-
?

Synonyms

Synonyms Comment Organism
BCO2
-
Homo sapiens
BCO2
-
Mus musculus
beta,beta-carotene-9',10'-dioxygenase
-
Homo sapiens
beta,beta-carotene-9',10'-dioxygenase
-
Mus musculus
xanthophyll cleavage enzyme
-
Homo sapiens
xanthophyll cleavage enzyme
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens
37
-
assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens
7.4
-
assay at Mus musculus

General Information

General Information Comment Organism
evolution the enzyme BCO2 is a member of the polyene oxygenase gene family. The major difference between human BCO2a enzyme and mouse BCO2 is the presence of 4 aa residues, GKAA, in human BCO2, suggesting the loss of an alternate splice site in the human gene. GKAA represents an extension of human BCO2 exon 3 caused by use of an alternate donor splice site. There has been considerable genetic drift since primate BCO2 first acquired the GKAA insertion and lost its xanthophyll cleavage function Homo sapiens
evolution the enzyme BCO2 is a member of the polyene oxygenase gene family. The major difference between human BCO2a enzyme and mouse BCO2 is the presence of 4 aa residues, GKAA, in human BCO2, suggesting the loss of an alternate splice site in the human gene. There has been considerable genetic drift since primate BCO2 first acquired the GKAA insertion and lost its xanthophyll cleavage function Mus musculus
malfunction BCO2 knockout mice, unlike wild-type mice, accumulate zeaxanthin in their retinas Mus musculus
physiological function in contrast to the human enzyme, mouse BCO2 is an active zeaxanthin cleavage enzyme. The binding affinities between human BCO2 and lutein, zeaxanthin, and meso-zeaxanthin are 10 to 40fold weaker than those for mouse BCO2, implying that ineffective capture of carotenoids by human BCO2 prevents cleavage of xanthophyll carotenoids Mus musculus
physiological function The major xanthophyll cleavage enzyme beta,beta-carotene-9',10'-dioxygenase (BCO2) is inactive in human retinas, explaining the unique accumulation of lutein, zeaxanthin, and meso-zeaxanthin in primate macula. In contrast to the murine enzyme, human BCO2 is not an active zeaxanthin cleavage enzyme. The binding affinities between human BCO2 and lutein, zeaxanthin, and meso-zeaxanthin are 10 to 40fold weaker than those for mouse BCO2, implying that ineffective capture of carotenoids by human BCO2 prevents cleavage of xanthophyll carotenoids. Primates uniquely concentrate xanthophyll carotenoids at high levels in retinal tissue Homo sapiens