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evolution
all enzymes in the family adopt a three-domain fold in which domains 1 and 2 resemble the fold of type II periplasmic binding proteins and the third domain, to which the cofactor is covalently attached, adopts a distinct alpha/beta topology
evolution
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all enzymes in the family adopt a three-domain fold in which domains 1 and 2 resemble the fold of type II periplasmic binding proteins and the third domain, to which the cofactor is covalently attached, adopts a distinct alpha/beta topology
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malfunction
acute intermittent porphyria is characterized by a partial deficiency in the enzyme, the third enzyme in heme biosynthesis
malfunction
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camouflage1 (cf1) mutant develops nonclonal, yellow-green sectors in leaves based on bundle sheath cell-specific death, yellow mutant regions show reduced levels of chlorophyll a + b, and total carotenoids, reduced photosynthesis and stomatal conductance compared to wild type and green regions of the mutant, constant light suppresses the cf1 sector formation, sectors only form during a limited time of leaf development, underlying is a decreased enzyme activity and increased levels of the substrate in green and yellow regions, yellow regions show an additional reduction in catalase activity
malfunction
enzyme deficiency results in overproduction of porphyrin precursors in acute intermittent porphyria
malfunction
enzyme deficiency results in overproduction of porphyrin precursors in acute intermittent porphyria
malfunction
half-maximal activity of the enzyme causes acute intermittent porphyria due to an error of heme biosynthesis
malfunction
mutation causes acute intermittent porphyria
malfunction
mutations cause acute intermittent porphyria
malfunction
autosomal dominantly inherited disease acute intermittent porphyria, AIP, is caused by mutations in hydroxymethylbilane synthase, phenotypes, overview
metabolism
third enzyme in heme biosynthesis
metabolism
third enzyme in heme biosynthesis pathway in mammals
metabolism
hydroxymethylbilane synthase is the third enzyme in the heme biosynthesis pathway
metabolism
porphobilinogen deaminase, an enzyme in the heme biosynthetic pathway, catalyzes the formation of a linear tetrapyrrole product, 1-hydroxymethylbilane, from four units of porphobilinogen
metabolism
the enzyme hydroxymethylbilane synthase catalyses a key early step of tetrapyrrole biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
metabolism
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the enzyme hydroxymethylbilane synthase catalyses a key early step of tetrapyrrole biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
metabolism
the enzyme hydroxymethylbilane synthase catalyses a key early step of the heme and chlorophyll biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
metabolism
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the enzyme hydroxymethylbilane synthase catalyses a key early step of tetrapyrrole biosynthesis pathways in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole
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physiological function
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early step in chlorophyll and heme biosynthesis
physiological function
overproduction of enzyme in Emericella nidulans promotes reactive nitrogen species tolerance, whereas repression causes growth that is hypersensitive to reactive nitrogen species. Hydroxymethylbilane synthase modulates the reduction of environmental NO and nitrite levels by flavohemoglobin and nitrite reductase
physiological function
porphobilinogen deaminase catalyzes the formation of 1-hydroxymethylbilane, a crucial intermediate in tetrapyrrole biosynthesis, through a step-wise polymerization of four molecules of porphobilinogen, using a unique dipyrromethane cofactor
physiological function
the addition of one molecule of porphobilinogen to the dipyrromethane cofactor is carried out in four steps: protonation of the substrate, porphobilinogen, deamination of porphobilinogen, electrophilic addition of the deaminated substrate to the terminal pyrrole ring of the enzyme-bound dipyrromethane cofactor and deprotonation of the carbon atom at the alpha-position of the second ring of dipyrromethane. Residue R26 is proposed to be the best suitable proton donor to the porphobilinogen moiety, which aids in the deamination of the substrate. During the electrophilic addition step, the intermediate formed is stabilized by the carboxylate side chain of the D99 residue. In the final deprotonation step, an extra proton from the second ring of dipyrromethane is transferred to R26 via the carboxylate side chain of D99, thus completing one cycle of the catalytic mechanism
additional information
molecular dynamics simulations for determmination of the exit mechanism of hydroxymethylbilane from the enzyme at the end of the catalytic cycle
additional information
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molecular dynamics simulations for determmination of the exit mechanism of hydroxymethylbilane from the enzyme at the end of the catalytic cycle