Sandbox Reserved 1097: Difference between revisions

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TYRP1 is a globular monomeric protein. It is composed of several domains: a short peptide signal on the N-terminal side followed by a large intra-melanosomal domain. This intra-melanosomal domain contain a rich-cysteine domain and a catalytic tyrosinase-like subdomain with two ion-binding sites.<ref name="Xlai">[Xuelei Lai, Harry J. Wichers, Montserrat Soler‐Lopez, Bauke W. Dijkstra. Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins. 2018 Jan 2 Epub 2017 Nov 28 PMID: 29052256 https://www.ncbi.nlm.nih.gov/pubmed/29052256 DOI: 10.1002/chem.201704410 https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201704410]</ref> The next part of the sequence is composed of a transmembrane alpha helix followed by a short cytoplasmic sequence on the C-terminal chain. <ref name = "decker"> [Decker. H, Tuczek.F. The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. 2017 Nov 13. Epub 2017 Oct 9 PMID: 28990327 https://www.ncbi.nlm.nih.gov/pubmed/28990327 DOI: 10.1002/anie.201708214 https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201708214]</ref>

The cystein-rich domain and the tyrosinase-like subdomain stongly interact together by the last loop of the cystein-rich domain preceding the N-terminal domain. The role of the cystein-rich domain is still unknown, it is only found in mammalians but 3D-structure highlights two pairs of short antiparallel beta-strands which create loops. This domain is stabilize by five disulfide bounds and is located at the opposite of the active site. It is sad that the cystein-rich domain might help to the formation of a complexe between TYR and TYRP2.<ref name="Xlai"/>

The cystein-rich domain and the tyrosinase-like subdomain stongly interact together by the last loop of the cystein-rich domain preceding the N-terminal domain. The role of the cystein-rich domain is still unknown, it is only found in mammalians but 3D-structure highlights two pairs of short antiparallel beta-strands which create loops. This domain is stabilize by five disulfide bounds and is located at the opposite of the active site. It is sad that the ~~cystein_rich~~ domain might help to the formation of a complexe between TYR and TYRP2.<ref name="Xlai"/>

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.

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These three proteins share similar active sites. Metal ions interact with three histidines.

==== 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.

Contrary to TYRP1 and TYRP2, TYR contains six sites of N-glycosylation.

The main difference between these three enzymes 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. Therefore these enzymes catalyze different reactions: TYR catalyzes the conversion of tyrosine into L-DOPA and then in Dopaquinone,TYRP2 isomerizes dopachrome to DHICA. Moreover, the active site of TYRP2 contains two molecules of water and a substrate interacting with both Zn2+ during reactions, whereas TYRP1 active site's contains only one molecule of water and a substrate which are interacting with only one Zn2+ ion. However, no 3D-structure of TYRP2 is now available so the exact coordination of metal ions in the active site stay unclear.<ref name="Xlai"/>

Contrary to TYRP1 and TYRP2, TYR contains six sites of N-glycosylation.<ref name="Xlai"/>

Sandbox Reserved 1097: Difference between revisions

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@@ Line 21: / Line 21: @@
 TYRP1 is a globular monomeric protein. It is composed of several domains: a short peptide signal on the N-terminal side followed by a large intra-melanosomal domain. This intra-melanosomal domain contain a rich-cysteine domain and a catalytic tyrosinase-like subdomain with two ion-binding sites.<ref name="Xlai">[Xuelei Lai, Harry J. Wichers, Montserrat Soler‐Lopez, Bauke W. Dijkstra. Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins. 2018 Jan 2 Epub 2017 Nov 28 PMID: 29052256 https://www.ncbi.nlm.nih.gov/pubmed/29052256 DOI: 10.1002/chem.201704410 https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201704410]</ref> The next part of the sequence is composed of a transmembrane alpha helix followed by a short cytoplasmic sequence on the C-terminal chain. <ref name = "decker"> [Decker. H, Tuczek.F. The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. 2017 Nov 13. Epub 2017 Oct 9 PMID: 28990327 https://www.ncbi.nlm.nih.gov/pubmed/28990327 DOI: 10.1002/anie.201708214 https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201708214]</ref>
+The cystein-rich domain and the tyrosinase-like subdomain stongly interact together by the last loop of the cystein-rich domain preceding the N-terminal domain. The role of the cystein-rich domain is still unknown, it is only found in mammalians but 3D-structure highlights two pairs of short antiparallel beta-strands which create loops. This domain is stabilize by five disulfide bounds and is located at the opposite of the active site. It is sad that the cystein-rich domain might help to the formation of a complexe between TYR and TYRP2.<ref name="Xlai"/>
-The cystein-rich domain and the tyrosinase-like subdomain stongly interact together by the last loop of the cystein-rich domain preceding the N-terminal domain. The role of the cystein-rich domain is still unknown, it is only found in mammalians but 3D-structure highlights two pairs of short antiparallel beta-strands which create loops. This domain is stabilize by five disulfide bounds and is located at the opposite of the active site. It is sad that the cystein_rich domain might help to the formation of a complexe between TYR and TYRP2.<ref name="Xlai"/>
 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.
@@ Line 49: / Line 48: @@
 These three proteins share similar active sites. Metal ions interact with three histidines.
 ==== 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.
-Contrary to TYRP1 and TYRP2, TYR contains six sites of N-glycosylation.
+The main difference between these three enzymes 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. Therefore these enzymes catalyze different reactions: TYR catalyzes the conversion of tyrosine into L-DOPA and then in Dopaquinone,TYRP2 isomerizes dopachrome to DHICA. Moreover, the active site of TYRP2 contains two molecules of water and a substrate interacting with both Zn2+ during reactions, whereas TYRP1 active site's contains only one molecule of water and a substrate which are interacting with only one Zn2+ ion. However, no 3D-structure of TYRP2 is now available so the exact coordination of metal ions in the active site stay unclear.<ref name="Xlai"/>
+Contrary to TYRP1 and TYRP2, TYR contains six sites of N-glycosylation.<ref name="Xlai"/>