Sandbox TYRP1: Difference between revisions
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=== Role in melanocytes === | === Role in melanocytes === | ||
First, TYRP1 has a role in melanin biosynthesis. Indeed, this enzyme has a catalytic function in the melanin biosynthetic pathway. In mouse, when a Cu2+ cation is bound, the protein catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. This protein is also able to catalyze the oxidation of 5,6-dihydroxyindole (DHI) into indole-5,6-quinone. Both products will allow to obtain eu-melanin, while pheo-melanin is obtain thanks to [https://www.uniprot.org/uniprot/P40126 TYRP2] activity <ref name= "koba"/>. The activity of the TYRP1 enzyme increase when the serine residues in position 505 and 509 are phosphorylated <ref name= "liu"/>. However, this mechanism does not happens in Humans because Human TYRP1 does not have the DHCIA activity. This can be | First, TYRP1 has a role in melanin biosynthesis. Indeed, this enzyme has a catalytic function in the melanin biosynthetic pathway. In mouse, when a Cu2+ cation is bound, the protein catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. This protein is also able to catalyze the oxidation of 5,6-dihydroxyindole (DHI) into indole-5,6-quinone. Both products will allow to obtain eu-melanin, while pheo-melanin is obtain thanks to [https://www.uniprot.org/uniprot/P40126 TYRP2] activity <ref name= "koba"/>. The activity of the TYRP1 enzyme increase when the serine residues in position 505 and 509 are phosphorylated <ref name= "liu"/>. However, this mechanism does not happens in Humans because Human TYRP1 does not have the DHCIA activity. This can be explained by the fact that the nature of ions in the active site is different. Indeed, two Zn2+ ions bound the active site of the TYRP1 enzyme instead of two Cu2+, which are responsible for a different activity <ref name= "lai"/>. In fact, the incorporation of Cu2+ instead of Zn2+ in human TYRP1 active site, gives to the enzyme the DHICA activity, but no experiment has shown that Cu2+ can replace Zn2+ in vivo conditions.<ref name="Xlai"/> To conclude, the exact role of TYRP1 in pigmentation remains still unclear. Moreover, no gene polymorphism has been observed among caucasian population, despite the variation of hair and skin colors <ref name= "box"/>. | ||
In addition, the [https://www.uniprot.org/uniprot/P07147 mouse homolog of the TYRP1] is involved in melanocytes differenciation too. Therefore, it could be used as a differentiation marker <ref name= "vija"/>. In humans, the exact role of TYRP1 in differentiation of melanocyte is unclear. However, it is supposed that the protein is involved in the mechanism, as it is involved in pigmentation. | In addition, the [https://www.uniprot.org/uniprot/P07147 mouse homolog of the TYRP1] is involved in melanocytes differenciation too. Therefore, it could be used as a differentiation marker <ref name= "vija"/>. In humans, the exact role of TYRP1 in differentiation of melanocyte is unclear. However, it is supposed that the protein is involved in the mechanism, as it is involved in pigmentation. | ||
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TYRP1 has six sites of N-glygosylation which are important for maturation of the protein (Asn 96, 104,181,304,350,385). On our 3D structure all these sites are glycosylated. | TYRP1 has six sites of N-glygosylation which are important for maturation of the protein (Asn 96, 104,181,304,350,385). On our 3D structure all these sites are glycosylated. | ||
The crystal structure of TYRP1 shows that TYRP1 can bind tyrosine, mimosine, kojic acid, tropolone. These substrates can bind to the enzyme thanks to aromatic stacking interactions with H381. The keto and hydroxy groups interact with Zinc ions and some hydrogen bonds are created with S394. | |||
=== The active site === | === The active site === | ||
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(image à faire) | (image à faire) | ||
According to crystal knowledges, it is said that TYRP1 and TYR can bind the same substrats. | |||
The three enzymes have several sites of N-glycosylation which are important for their maturation, two of these sites are shared by the three enzymes. TYRP1 and 2 have both six sites and among them, four are exactly the same. <ref name="Xlai"/> | The three enzymes have several sites of N-glycosylation which are important for their maturation, two of these sites are shared by the three enzymes. TYRP1 and 2 have both six sites and among them, four are exactly the same. <ref name="Xlai"/> | ||
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==== Differences: ==== | ==== Differences: ==== | ||
The main difference between these three enzyme is the nature of metal ions they bind on the active site. TYRP1 and TYRP2 bind two zinc ions whereas TYR binds two copper ions. | The main difference between these three enzyme is the nature of metal ions they bind on the active site. TYRP1 and TYRP2 bind two zinc ions whereas TYR binds two copper ions. | ||
Contrary to TYRP1 and TYRP2, TYR contains six sites of N- | Contrary to TYRP1 and TYRP2, TYR contains six sites of N-glycosylation. | ||