Tyrosinase - Revision history

Michal Harel at 11:17, 24 December 2020

Michal Harel — Thu, 24 Dec 2020 11:17:11 GMT

←Older revision		Revision as of 11:17, 24 December 2020
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	== Function ==		== Function ==
-	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone.<br />	+	'''Tyrosinase''' or '''monophenol monooxygenase''' or '''polyphenol oxidase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone.<br />
	'''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. <br />		'''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. <br />
	'''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.		'''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.

Michal Harel at 09:11, 16 March 2020

Michal Harel — Mon, 16 Mar 2020 09:11:28 GMT

←Older revision		Revision as of 09:11, 16 March 2020
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	</StructureSection>		</StructureSection>
-	== 3D Structures of tyrosinase ==

-	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-	{{#tree:id=OrganizedByTopic\|openlevels=0\|
-
-	*Tyrosinase
-
-	**[[4oua]] – Tyr PPO4 + Cu - mushroom <br />
-	**[[5ce9]] – Tyr + Cu - walnut <br />
-	**[[2zwg]], [[2zwe]], [[2zwf]] – ScTyr + caddie protein + L-tyrosine + Cu – ''Streptomyces castaneoglobisporus''<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 />
-	**[[2ahk]], [[2ahl]], [[2zmx]], [[2zmy]], [[2zmz]], [[2zwd]], [[3aws]], [[3awt]], [[3awu]], [[3awv]], [[3aww]] – ScTyr + caddie protein + Cu <br />
-	**[[3awx]], [[3awy]], [[3awz]], [[3ax0]] – ScTyr + caddie protein (mutant) + Cu <br />
-	**[[3nm8]], [[3npy]] – BmTyr + Zn + Cu – ''Bacillus megaterium''<br />
-	**[[3nq5]] – BmTyr (mutant) + Zn + Cu <br />
-	**[[3nq0]], [[3ntm]] – BmTyr + Cu <br />
-	**[[4hd4]], [[4hd6]], [[4hd7]], [[4j6t]], [[4j6u]], [[4j6v]] – BmTyr (mutant) + Cu <br />
-	**[[5i38]] – BmTyr + Cu + kojic acid<br />
-	**[[3nq1]] – BmTyr + Zn + Cu + kojic acid<br />
-	**[[4d87]] – BmTyr + Cu + SDS<br />
-	**[[6qxd]] – BmTyr + Cu + inhibitor<br />
-	**[[4p6r]] – BmTyr + Zn + tyrosine <br />
-	**[[4p6s]] – BmTyr + Zn + L-tyrosine <br />
-	**[[4p6t]] – BmTyr + Cu + p-tyrosol <br />
-	**[[5i38]], [[5oae]], [[6ei4]] – BmTyr + Cu + inhibitor <br />
-	**[[5i3a]], [[5i3b]] – BmTyr + Zn + inhibitor <br />
-	**[[3w6q]] – AoTyr – ''Aspergillus oryzae'' <br />
-	**[[3w6w]] – AoTyr + Cu <br />
-	**[[6j2u]] – Tyr + Tyr co-factor protein + Zn – ''Streptomyces avermitilis''<br />
-	**[[5zre]], [[5zrd]] – Tyr + O + Zn – ''Burkholderia thailandensis''<br />
-
-	*β-tyrosinase or tyrosine phenol-lyase
-
-	**[[1tpl]] – CiBTyr – ''Citrobacter intermedius'' <br />
-	**[[2tpl]] – CiTyr + Cs + pyridoxal phosphate + hydroxyphenyl propionate <br />
-	**[[1c7g]] – Tyr + pyridoxal phosphate – ''Erwinia herbicola''<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 />
-	**[[2yhk]] – CfBTyr (mutant) + pyridoxal phosphate<br />
-	**[[2vlf]], [[2vlh]], [[2yct]] – CfBTyr + 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 or polyphenol oxidase
-
-	**[[6els]] – Tyr3 + O + Cu – apple<br />
-	**[[2y9w]] – AbTyr3 + lectin-like fold protein + Cu – ''Agaricus bisporus'' <br />
-	**[[2y9x]] – AbTyr3 + lectin-like fold protein + Cu + tropolone<br />
-
-	*Tyrosinase 4
-
-	**[[5m6b]] – Tyr4 + Cu – button mushroom <br />
-	}}
	[[Category:Topic Page]]		[[Category:Topic Page]]
	== References ==		== References ==
	<references/>		<references/>

Michal Harel at 09:10, 16 March 2020

Michal Harel — Mon, 16 Mar 2020 09:10:25 GMT

←Older revision		Revision as of 09:10, 16 March 2020
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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 />

Michal Harel at 07:51, 16 March 2020

Michal Harel — Mon, 16 Mar 2020 07:51:06 GMT

←Older revision		Revision as of 07:51, 16 March 2020
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	== Function ==		== Function ==
-	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone.	+	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone.<br />
-	'''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3.	+	'''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. <br />
	'''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.		'''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.

Michal Harel at 07:50, 16 March 2020

Michal Harel — Mon, 16 Mar 2020 07:50:38 GMT

←Older revision		Revision as of 07:50, 16 March 2020
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	== Function ==		== Function ==
-	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone. '''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. '''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.	+	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone.
		+	'''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3.
		+	'''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.

	== Relevance ==		== Relevance ==

-	Tyr inhibitors are used in dermatological treatments and in cosmetics.	+	Tyr inhibitors are used in dermatological treatments and in cosmetics<ref>PMID:17605157</ref>.

	== Disease ==		== Disease ==

Michal Harel at 07:48, 16 March 2020

Michal Harel — Mon, 16 Mar 2020 07:48:24 GMT

←Older revision		Revision as of 07:48, 16 March 2020
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	== Function ==		== Function ==
-	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone~~. Tyr inhibitors are used in dermatological treatments and in cosmetics~~. '''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. '''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.	+	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone. '''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. '''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.
		+
		+	== Relevance ==
		+
		+	Tyr inhibitors are used in dermatological treatments and in cosmetics.

	== Disease ==		== Disease ==

Michal Harel at 10:54, 3 November 2019

Michal Harel — Sun, 03 Nov 2019 10:54:03 GMT

←Older revision		Revision as of 10:54, 3 November 2019
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	== Function ==		== Function ==
-	'''Tyrosinase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone. Tyr inhibitors are used in dermatological treatments and in cosmetics. '''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. '''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.	+	'''Tyrosinase''' or '''monophenol monooxygenase''' (Tyr) is a copper-containing enzyme which catalyzes the production of melanin and other pigments by oxidation of tyrosine. Tyr is involved in the hydroxylation of monophenol and the conversion of o-diphenol to o-quinone. Tyr inhibitors are used in dermatological treatments and in cosmetics. '''β-Tyr''' (BTyr) or '''tyrosine phenol-lyase''' hydrolyzes tyrosine to phenol, pyruvate and NH3. '''Tyr 3''' (Tyr3) or '''polyphenol oxidase''' catalyzes the hydroxylation of monophenols to diphenols.

	== Disease ==		== Disease ==

Michal Harel at 21:22, 28 September 2018

Michal Harel — Fri, 28 Sep 2018 21:22:27 GMT

←Older revision		Revision as of 21:22, 28 September 2018
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	**[[4p6s]] – BmTyr + Zn + L-tyrosine <br />		**[[4p6s]] – BmTyr + Zn + L-tyrosine <br />
	**[[4p6t]] – BmTyr + Cu + p-tyrosol <br />		**[[4p6t]] – BmTyr + Cu + p-tyrosol <br />
-	**[[5i38]] – BmTyr + Cu + inhibitor <br />	+	**[[5i38]], [[5oae]], [[6ei4]] – BmTyr + Cu + inhibitor <br />
	**[[5i3a]], [[5i3b]] – BmTyr + Zn + inhibitor <br />		**[[5i3a]], [[5i3b]] – BmTyr + Zn + inhibitor <br />
	**[[3w6q]] – AoTyr – ''Aspergillus oryzae'' <br />		**[[3w6q]] – AoTyr – ''Aspergillus oryzae'' <br />

Joel L. Sussman at 03:58, 16 October 2017

Joel L. Sussman — Mon, 16 Oct 2017 03:58:17 GMT

←Older revision		Revision as of 03:58, 16 October 2017
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-	<StructureSection load='' size='340' side='right' caption='Tyrosinase complex with tyrosine and Zn+2 ion (grey) (PDB code [[4p6r]])' scene=''>	+	<StructureSection load='4p6r' size='340' side='right' caption='Tyrosinase complex with tyrosine and Zn+2 ion (grey) (PDB code [[4p6r]])' scene=''>

Joel L. Sussman at 03:57, 16 October 2017

Joel L. Sussman — Mon, 16 Oct 2017 03:57:44 GMT

←Older revision		Revision as of 03:57, 16 October 2017
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-	<StructureSection load='~~4p6r~~' size='340' side='right' caption='Tyrosinase complex with tyrosine and Zn+2 ion (grey) (PDB code [[4p6r]])' scene=''>	+	<StructureSection load='' size='340' side='right' caption='Tyrosinase complex with tyrosine and Zn+2 ion (grey) (PDB code [[4p6r]])' scene=''>