Literature summary for 1.14.11.2 extracted from

Kivirikko, K.I.; Myllyl�, R.
The hydroxylation of prolyl and lysyl residues (1980), Enzymol. Post- transl. Modif. Proteins (Freedman, R. B. , Hawkins, H. C. , eds. ) Academic Press, New York, 1, 53-104.

No PubMed abstract available

Search for more literature for 1.14.11.2

Activating Compound

Activating Compound	Comment	Organism
bovine serum albumin	activation	Gallus gallus
bovine serum albumin	activation	Homo sapiens
bovine serum albumin	activation	Rattus norvegicus
catalase	activation	Gallus gallus
catalase	activation	Homo sapiens
catalase	activation	Rattus norvegicus
dithiothreitol	activation	Gallus gallus
dithiothreitol	activation	Homo sapiens
dithiothreitol	activation	Rattus norvegicus

Inhibitors

Inhibitors	Comment	Organism
(Gly-Pro-Gly)n	competitive inhibitors with respect to the polypeptide substrate	Gallus gallus
(Gly-Pro-Gly)n	competitive inhibitors with respect to the polypeptide substrate	Homo sapiens
(Pro-Ala-Gly)n	competitive inhibitors with respect to the polypeptide substrate	Gallus gallus
(Pro-Ala-Gly)n	competitive inhibitors with respect to the polypeptide substrate	Homo sapiens
bradykinin analogs	especially those in which the proline in the -X-Pro-Gly- triplet is replaced by certain proline analogues, the addition of a glutamyl residue to the N-terminal end of 3,4-dehydroprolyl- or trans-4-hydroxyprolyl-bradykinin considerably increases their effectiveness	Gallus gallus
bradykinin analogs	especially those in which the proline in the -X-Pro-Gly- triplet is replaced by certain proline analogues, the addition of a glutamyl residue to the N-terminal end of 3,4-dehydroprolyl- or trans-4-hydroxyprolyl-bradykinin considerably increases their effectiveness	Homo sapiens
catechol analogues	inhibitor of the reaction due in part to the chelation of Fe2+	Gallus gallus
catechol analogues	inhibitor of the reaction due in part to the chelation of Fe2+	Homo sapiens
dilantin	inhibitor of the reaction due in part to the chelation of Fe2+	Gallus gallus
dilantin	inhibitor of the reaction due in part to the chelation of Fe2+	Homo sapiens
hydralazine	inhibitor of the reaction due in part to the chelation of Fe2+	Gallus gallus
hydralazine	inhibitor of the reaction due in part to the chelation of Fe2+	Homo sapiens
nitroblue tetrazolium	is capable of scavenging superoxide, competitive inhibitor with respect to O2	Gallus gallus
nitroblue tetrazolium	is capable of scavenging superoxide, competitive inhibitor with respect to O2	Homo sapiens
poly(L-proline)	competitive inhibitors with respect to the polypeptide substrate, the inhibition increases with chain length	Gallus gallus
poly(L-proline)	competitive inhibitors with respect to the polypeptide substrate, the inhibition increases with chain length	Homo sapiens
tetracyclin	inhibitor of the reaction due in part to the chelation of Fe2+	Gallus gallus
tetracyclin	inhibitor of the reaction due in part to the chelation of Fe2+	Homo sapiens
Zn2+	-	Gallus gallus
Zn2+	-	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
additional information	-	additional information	effect of amino acids in other parts of the peptide chain, effect of peptide chain length and asymmetry in the hydroxylation of (Pro-Pro-Gly)n	Gallus gallus
additional information	-	additional information	effect of amino acids in other parts of the peptide chain, effect of peptide chain length and asymmetry in the hydroxylation of (Pro-Pro-Gly)n	Homo sapiens
0.005	-	2-oxoglutarate	biological substrate	Gallus gallus
0.022	-	2-oxoglutarate	synthetic substrate	Gallus gallus
0.043	-	O2	synthetic substrate	Gallus gallus

Metals/Ions

Metals/Ions	Comment	Organism
Fe2+	-	Homo sapiens
Fe2+	-	Rattus norvegicus
Fe2+	Km with biological substrate: 0.002 mM, Km with synthetic substrate: 0.004 mM	Gallus gallus
Fe2+	very specific requirement, Fe2+ is apparently not firmly bound, the enzyme may bind 4 mol of Fe2+ at its maximum activity, there is a positive co-operativity in this binding, binding may occur to one or more SH-groups	Gallus gallus

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
230000	240000	gel filtration	Homo sapiens
230000	240000	gel filtration	Rattus norvegicus
230000	240000	sedimentation equilibrium centrifugation	Gallus gallus

Organism

Organism	UniProt	Comment	Textmining
Gallus gallus	-	-	-
Homo sapiens	-	-	-
Rattus norvegicus	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
glycoprotein	-	Gallus gallus
glycoprotein	-	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
using affinity chromatography on a column containing a polypeptide substrate of the enzyme linked to agarose, elution of the enzyme with a second peptide substrate and separation of the enzyme from this peptide by gel filtration	Gallus gallus
using affinity chromatography on a column containing a polypeptide substrate of the enzyme linked to agarose, elution of the enzyme with a second peptide substrate and separation of the enzyme from this peptide by gel filtration	Rattus norvegicus
using affinity chromatography on a column containing poly-(L-proline) linked to agarose, elution with the same polypeptide of a lower molecular weight, and gel filtration	Gallus gallus
using affinity chromatography on a column containing poly-(L-proline) linked to agarose, elution with the same polypeptide of a lower molecular weight, and gel filtration	Homo sapiens
using affinity chromatography on a column containing poly-(L-proline) linked to agarose, elution with the same polypeptide of a lower molecular weight, and gel filtration	Rattus norvegicus
using fractionating precipitation, ion-exchange chromatography and gel filtration	Gallus gallus
using fractionating precipitations, ion-exchange chromatographies and gel filtrations	Rattus norvegicus

Reaction

Reaction	Comment	Organism	Reaction ID
procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2	mechanism	Gallus gallus	a
procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2	mechanism	Homo sapiens	a

Source Tissue

Source Tissue	Comment	Organism	Textmining
cartilage	embryo	Gallus gallus	-
embryo	tendon cell, cartilage, skin, spleen	Gallus gallus	-
fetus	-	Rattus norvegicus	-
fetus	skin	Homo sapiens	-
liver	-	Gallus gallus	-
liver	-	Homo sapiens	-
liver	-	Rattus norvegicus	-
skin	-	Homo sapiens	-
skin	-	Rattus norvegicus	-
skin	embryo	Gallus gallus	-
spleen	embryo	Gallus gallus	-
tendon	embryo	Gallus gallus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
proline containing peptide + 2-oxoglutarate + O2	-	Rattus norvegicus	4-hydroxyproline containing peptide + succinate + CO2	-	?
proline containing peptide + 2-oxoglutarate + O2	no hydroxylation of free proline, minimum sequence required X-Pro-Gly, best substrates are those where Pro precedes Gly, which can be substituted by Ala or beta-alanine. The amino acid preceding Pro can be Pro, Ala, Leu, Arg, Val, Glu, but not Gly or Ser. Additionally the sequence, the conformation and the peptide chain length influence the rate of hydroxylation	Gallus gallus	4-hydroxyproline containing peptide + succinate + CO2	-	?
proline containing peptide + 2-oxoglutarate + O2	no hydroxylation of free proline, minimum sequence required X-Pro-Gly, best substrates are those where Pro precedes Gly, which can be substituted by Ala or beta-alanine. The amino acid preceding Pro can be Pro, Ala, Leu, Arg, Val, Glu, but not Gly or Ser. Additionally the sequence, the conformation and the peptide chain length influence the rate of hydroxylation	Homo sapiens	4-hydroxyproline containing peptide + succinate + CO2	-	?
proline containing peptide + 2-oxoglutarate + O2	the presence of 2-oxoglutarate is an absolute and highly specific requirement, the formation of 4-hydroxyproline is accompanied by a stoichiometric decarboxylation of 2-oxoglutarate, the oxygen of the hydroxyl group is derived from molecular oxygen, the other atom of the O2 molecule being incorporated into the succinate, the activated form of oxygen is probably superoxide	Gallus gallus	4-hydroxyproline containing peptide + succinate + CO2	-	?
proline containing peptide + 2-oxoglutarate + O2	the presence of 2-oxoglutarate is an absolute and highly specific requirement, the formation of 4-hydroxyproline is accompanied by a stoichiometric decarboxylation of 2-oxoglutarate, the oxygen of the hydroxyl group is derived from molecular oxygen, the other atom of the O2 molecule being incorporated into the succinate, the activated form of oxygen is probably superoxide	Homo sapiens	4-hydroxyproline containing peptide + succinate + CO2	-	?

Subunits

Subunits	Comment	Organism
More	structure of the tetramer, physicochemical properties of the subunits	Gallus gallus
More	structure of the tetramer, physicochemical properties of the subunits	Homo sapiens
tetramer	alpha2 beta2, alpha: 64000, beta: 60000, ratio 1 to 1, SDS-PAGE	Gallus gallus
tetramer	alpha2 beta2, alpha: 64000, beta: 60000, ratio 1 to 1, SDS-PAGE	Homo sapiens
tetramer	alpha2 beta2, alpha: 64000, beta: 60000, ratio 1 to 1, SDS-PAGE	Rattus norvegicus

Cofactor

Cofactor	Comment	Organism
ascorbate	requirement	Gallus gallus
ascorbate	requirement	Homo sapiens
ascorbate	requirement	Rattus norvegicus
ascorbate	probably required to prevent oxidation of the enzyme-bound Fe2+ or free enzyme between catalytic cycles, replaceability by certain reduced pteridines and thiols. Km with biological substrate: 0.1 mM, Km with synthetic substrate: 0.3 mM	Gallus gallus
ascorbate	probably required to prevent oxidation of the enzyme-bound Fe2+ or free enzyme between catalytic cycles, replaceability by certain reduced pteridines and thiols. Km with biological substrate: 0.1 mM, Km with synthetic substrate: 0.3 mM	Homo sapiens
ascorbate	pure enzyme, high specificity, dithiothreitol and L-cysteine are the only compounds that give more than 10% of the activity found with the optimal ascorbate concentration, some reduced pteridines give values ranging from 3 to 9%	Gallus gallus