Tyrosinase

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Substitution of Asn205 to Ala or Asp residues resulted in significant reduction in copper uptake and enzymatic activity. In the crystal structure of variant N205D (PDB [[4j6v]]), residue <scene name='55/558329/Cv/20'>Asp205 is turned towards Arg209 and therefore cannot form a polar bond with His204</scene>.
Substitution of Asn205 to Ala or Asp residues resulted in significant reduction in copper uptake and enzymatic activity. In the crystal structure of variant N205D (PDB [[4j6v]]), residue <scene name='55/558329/Cv/20'>Asp205 is turned towards Arg209 and therefore cannot form a polar bond with His204</scene>.
Furthermore, Phe197, Met61 and Met184, which are also located at the entrance to the active site, were found to play an important role in Cu uptake. Substitution of a bulky Phe197 to Ala, resulted in higher Cu uptake, while mutations at positions 61 and 184, had an opposite effect. <scene name='55/558329/Cv/18'>The active site of variant F197A</scene> ([[4j6t]]). <span style="color:lime;background-color:black;font-weight:bold;">Six His residues composing the active site are colored in green</span> and are ligating CuA and CuB ions which are shown as spheres. <span style="color:yellow;background-color:black;font-weight:bold;">Alanine residue at position 197 is colored in yellow</span>. In addition, it was found that these residues are also important for enhancing the diphenolase activity of the enzyme. Therefore, we can suggest that a Cu ion entering the active site (CuA) first associates with the methionine residues followed by its transfer to His60 in its flipped out conformation. Following Cu binding, His60 alters its conformation and transfers CuA into the active site in a paddle-like motion. We propose that CuB passes only through Asp205 and Phe197. The proposed pathway clarifies the previously reported observations of TyrBm’s tighter binding of CuA in comparison to CuB.
Furthermore, Phe197, Met61 and Met184, which are also located at the entrance to the active site, were found to play an important role in Cu uptake. Substitution of a bulky Phe197 to Ala, resulted in higher Cu uptake, while mutations at positions 61 and 184, had an opposite effect. <scene name='55/558329/Cv/18'>The active site of variant F197A</scene> ([[4j6t]]). <span style="color:lime;background-color:black;font-weight:bold;">Six His residues composing the active site are colored in green</span> and are ligating CuA and CuB ions which are shown as spheres. <span style="color:yellow;background-color:black;font-weight:bold;">Alanine residue at position 197 is colored in yellow</span>. In addition, it was found that these residues are also important for enhancing the diphenolase activity of the enzyme. Therefore, we can suggest that a Cu ion entering the active site (CuA) first associates with the methionine residues followed by its transfer to His60 in its flipped out conformation. Following Cu binding, His60 alters its conformation and transfers CuA into the active site in a paddle-like motion. We propose that CuB passes only through Asp205 and Phe197. The proposed pathway clarifies the previously reported observations of TyrBm’s tighter binding of CuA in comparison to CuB.
 +
== 3D Structures of tyrosinase ==
 +
[[Tyrosinase 3D structures]]
</StructureSection>
</StructureSection>
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*Tyrosinase
*Tyrosinase
 +
**[[4oua]] – Tyr PPO4 + Cu - mushroom <br />
 +
**[[5ce9]] – Tyr + Cu - walnut <br />
**[[2zwg]], [[2zwe]], [[2zwf]] – ScTyr + caddie protein + L-tyrosine + Cu – ''Streptomyces castaneoglobisporus''<br />
**[[2zwg]], [[2zwe]], [[2zwf]] – ScTyr + caddie protein + L-tyrosine + Cu – ''Streptomyces castaneoglobisporus''<br />
**[[1wx2]], [[1wx4]] – ScTyr + caddie protein + peroxide + Cu <br />
**[[1wx2]], [[1wx4]] – ScTyr + caddie protein + peroxide + Cu <br />
 +
**[[5z0m]], [[5z0l]], [[5z0k]], [[5z0d]], [[5z0e]], [[5z0f]], [[5z0g]], [[5z0h]], [[5z0i]], [[5z0j]] – ScTyr + caddie protein + L-dopa + Cu + Phe derivative<br />
**[[1wx5]], [[1wxc]] – ScTyr + caddie protein <br />
**[[1wx5]], [[1wxc]] – ScTyr + caddie protein <br />
**[[2ahk]], [[2ahl]], [[2zmx]], [[2zmy]], [[2zmz]], [[2zwd]], [[3aws]], [[3awt]], [[3awu]], [[3awv]], [[3aww]] – ScTyr + caddie protein + Cu <br />
**[[2ahk]], [[2ahl]], [[2zmx]], [[2zmy]], [[2zmz]], [[2zwd]], [[3aws]], [[3awt]], [[3awu]], [[3awv]], [[3aww]] – ScTyr + caddie protein + Cu <br />
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**[[3nq1]] – BmTyr + Zn + Cu + kojic acid<br />
**[[3nq1]] – BmTyr + Zn + Cu + kojic acid<br />
**[[4d87]] – BmTyr + Cu + SDS<br />
**[[4d87]] – BmTyr + Cu + SDS<br />
 +
**[[6qxd]] – BmTyr + Cu + inhibitor<br />
**[[4p6r]] – BmTyr + Zn + tyrosine <br />
**[[4p6r]] – BmTyr + Zn + tyrosine <br />
**[[4p6s]] – BmTyr + Zn + L-tyrosine <br />
**[[4p6s]] – BmTyr + Zn + L-tyrosine <br />
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**[[3w6q]] – AoTyr – ''Aspergillus oryzae'' <br />
**[[3w6q]] – AoTyr – ''Aspergillus oryzae'' <br />
**[[3w6w]] – AoTyr + Cu <br />
**[[3w6w]] – AoTyr + Cu <br />
-
**[[4oua]] – Tyr PPO4 + Cu - mushroom <br />
+
**[[6j2u]] – Tyr + Tyr co-factor protein + Zn – ''Streptomyces avermitilis''<br />
-
**[[5ce9]] – Tyr + Cu - walnut <br />
+
**[[5zre]], [[5zrd]] – Tyr + O + Zn – ''Burkholderia thailandensis''<br />
-
*β-tyrosinase
+
*β-tyrosinase or tyrosine phenol-lyase
**[[1tpl]] – CiBTyr – ''Citrobacter intermedius'' <br />
**[[1tpl]] – CiBTyr – ''Citrobacter intermedius'' <br />
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**[[1c7g]] – Tyr + pyridoxal phosphate – ''Erwinia herbicola''<br />
**[[1c7g]] – Tyr + pyridoxal phosphate – ''Erwinia herbicola''<br />
**[[2ez2]] – CfBTyr – ''Citrobacter freundii'' <br />
**[[2ez2]] – CfBTyr – ''Citrobacter freundii'' <br />
 +
**[[6mqq]], [[6mme]], [[6dur]] – CfBTyr + pyridine derivatives<br />
 +
**[[6dz5]], [[6dxv]], [[6dvx]] – CfBTyr (mutant) + pyridine derivatives<br />
**[[2ez1]] – CfBTyr + pyridoxal phosphate <br />
**[[2ez1]] – CfBTyr + pyridoxal phosphate <br />
**[[2yhk]] – CfBTyr (mutant) + pyridoxal phosphate<br />
**[[2yhk]] – CfBTyr (mutant) + pyridoxal phosphate<br />
**[[2vlf]], [[2vlh]], [[2yct]] – CfBTyr + pyridoxal phosphate derivative<br />
**[[2vlf]], [[2vlh]], [[2yct]] – CfBTyr + pyridoxal phosphate derivative<br />
**[[2ycn]], [[2ycp]] – CfBTyr (mutant) + pyridoxal phosphate derivative<br />
**[[2ycn]], [[2ycp]] – CfBTyr (mutant) + pyridoxal phosphate derivative<br />
 +
**[[6nv8]], [[6mo3]], [[6mls]] – CfBTyr + pyridoxal phosphate derivative + pyridine derivative<br />
 +
**[[6ecg]], [[6dyt]] – CfBTyr (mutant) + pyridoxal phosphate derivative + pyridine derivative<br />
 +
**[[6mpd]] – CfBTyr + pyridoxal phosphate derivative + pyridine derivative + fluoro-Tyr<br />
-
*Tyrosinase 3
+
*Tyrosinase 3 or polyphenol oxidase
 +
**[[6els]] – Tyr3 + O + Cu – apple<br />
**[[2y9w]] – AbTyr3 + lectin-like fold protein + Cu – ''Agaricus bisporus'' <br />
**[[2y9w]] – AbTyr3 + lectin-like fold protein + Cu – ''Agaricus bisporus'' <br />
**[[2y9x]] – AbTyr3 + lectin-like fold protein + Cu + tropolone<br />
**[[2y9x]] – AbTyr3 + lectin-like fold protein + Cu + tropolone<br />

Revision as of 09:10, 16 March 2020

Tyrosinase complex with tyrosine and Zn+2 ion (grey) (PDB code 4p6r)

Drag the structure with the mouse to rotate

3D Structures of tyrosinase

Updated on 16-March-2020

References

  1. ↑ Parvez S, Kang M, Chung HS, Bae H. Naturally occurring tyrosinase inhibitors: mechanism and applications in skin health, cosmetics and agriculture industries. Phytother Res. 2007 Sep;21(9):805-16. doi: 10.1002/ptr.2184. PMID:17605157 doi:http://dx.doi.org/10.1002/ptr.2184
  2. ↑ Kanteev M, Goldfeder M, Chojnacki M, Adir N, Fishman A. The mechanism of copper uptake by tyrosinase from Bacillus megaterium. J Biol Inorg Chem. 2013 Dec;18(8):895-903. doi: 10.1007/s00775-013-1034-0. Epub, 2013 Sep 6. PMID:24061559 doi:http://dx.doi.org/10.1007/s00775-013-1034-0

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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