Proteopedia - User contributions [en]

Copper Amine Oxidase

2011-04-07T07:23:35Z

Raymond Lyle:

__TOC__
{{STRUCTURE_2d1w | PDB=2d1w | SCENE= }}
== Structure ==
[[Image:TTS.png|thumb|left|alt=3-((3E)-4-HYDROXY-3-{[2-(4-HYDROXYPHENYL)ETHYL]IMINO}-6-OXOCYCLOHEXA-1,4-DIEN-1-YL)ALANINE.|Residue 382 is a tyrosine residue, modified into topa-quinone, shown here bound to tyramine.]] 2d1w is the tyramine-bound substrate Schiff-base intermediate of [http://en.wikipedia.org/wiki/Amine_oxidase_%28copper-containing%29 copper amine oxidase] derived from [http://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis]. Copper amine oxidases are classified as EC 1.4.3.6 in the EC number classification system of enzymes, and they belong to the larger class of [http://en.wikipedia.org/wiki/Oxidoreductase oxidoreductases]. The structure of this enzyme was determined by Murakawa ''et al.'' in 2005, by x-ray diffraction<ref name="Murakawa">PMID:16487484</ref>. It consists of a disulfide-linked homodimer, with each subunit containing 638 residues. Each subunit also contains a <scene name='Sandbox_Reserved_331/Copper_ligand/5'>copper ligand</scene> near the active site, which is coordinated by three histidine residues. Located near the Cu<sup>2+</sup> ligand is a tyrosine residue that has been modified into topa-quinone, which is also a cofactor in all other copper amine oxidases<ref name="Parsons">PMID:8591028</ref>. The active site of the enzyme is located near the center of the homodimer, which is connected to the outside of the enzyme by an extensively hydrated channel. It is suspected that the water helps to carry O<sub>2</sub> to the active site, as well as being used in the reaction itself<ref name="Mure">PMID:12135347</ref>.
<div style="clear:left;"></div>

== Reaction Mechanism ==
Copper amine oxidase catalyzes the oxidation of a primary amine to the corresponding aldehyde, yielding hydrogen peroxide and free ammonia. An example of this is the oxidation of [http://en.wikipedia.org/wiki/Tyramine tyramine]:

[[Image:Tyramine oxidation.png|thumb|center|600px|The oxidation of tyramine, yielding the corresponding aldehyde, hydrogen peroxide, and ammonia.]]
<div style="clear:left;"></div>

=== Reductive half-reaction ===
In the reductive half-reaction, the carbonyl of topa-quinone reacts with the primary amine of the substrate, forming the substrate Schiff-base intermediate ([http://www.proteopedia.org/wiki/index.php/2cwv 2cwv]). The α-proton is then abstracted by a conserved aspartic acid residue (Asp298), which forms the product Schiff-base intermediate ([http://www.proteopedia.org/wiki/index.php/2cwv 2cwv]). Several studies have shown that the abstraction of the α-proton proceeds through [http://en.wikipedia.org/wiki/Quantum_tunnelling quantum-mechanical tunneling], which allows the proton to pass through an energy barrier which it would otherwise not be able to pass according to classical mechanics<ref name="Murakawa" /><ref name="Grant">PMID:2790014</ref>.This bond is then hydrolyzed, which yields the aldehyde form of the substrate, the aminoquinol form of topa-quinone, and a proton.
[[Image:2d1wReductive Half.png|thumb|center|800px|The reductive half-reaction in the oxidation of a primary amine by copper amine oxidase.]]
<div style="clear:left;"></div>

=== Oxidative half-reaction ===
In the oxidative half-reaction, electrons are transferred from the reduced form of topa-quinone to O<sub>2</sub>, forming a superoxide ion that is stabilized by the Cu<sup>2+</sup> ligand. Reduction of the superoxide by the amino-quinone form of topa-quinone yields peroxide and the imino-quinone form, leading to the release of hydrogen peroxide. Hydrolysis of the imino-quinone form of topa-quinone then releases free ammonia, and regenerates the oxidized form of topa-quinone<ref name="Grant" />.
[[Image:2d1w Oxidative Half.png|thumb|center|800px|The oxidative half-reaction, in which topa-quinone is restored to its oxidized form, releasing ammonia and hydrogen peroxide.]]
<div style="clear:left;"></div>
= Additional Resources =
*[http://www.pdb.org/pdb/explore/explore.do?structureId=2D1W Entry 2D1W in the RCSB Protein Data Bank]
*[http://www.google.ca/url?sa=t&source=web&cd=2&ved=0CB8QFjAB&url=http%3A%2F%2Fwww.jbc.org%2Fcontent%2F271%2F9%2F4718.full.pdf&rct=j&q=Topa%20quinone&ei=lb6UTZyZH8PdiAKF9t39CA&usg=AFQjCNFe66G0M8KGm8HD9rmSgzSyZwi9RQ&sig2=nwPWJNlka1WrmFatRPFH9Q&cad=rja The Biosynthesis of Topa Quinone Cofactor in Bacterial Amine Oxidases]

= References =

<references />

Copper Amine Oxidase

2011-04-07T07:23:01Z

Raymond Lyle:

=Copper Amine Oxidase=
__TOC__
{{STRUCTURE_2d1w | PDB=2d1w | SCENE= }}
== Structure ==
[[Image:TTS.png|thumb|left|alt=3-((3E)-4-HYDROXY-3-{[2-(4-HYDROXYPHENYL)ETHYL]IMINO}-6-OXOCYCLOHEXA-1,4-DIEN-1-YL)ALANINE.|Residue 382 is a tyrosine residue, modified into topa-quinone, shown here bound to tyramine.]] 2d1w is the tyramine-bound substrate Schiff-base intermediate of [http://en.wikipedia.org/wiki/Amine_oxidase_%28copper-containing%29 copper amine oxidase] derived from [http://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis]. Copper amine oxidases are classified as EC 1.4.3.6 in the EC number classification system of enzymes, and they belong to the larger class of [http://en.wikipedia.org/wiki/Oxidoreductase oxidoreductases]. The structure of this enzyme was determined by Murakawa ''et al.'' in 2005, by x-ray diffraction<ref name="Murakawa">PMID:16487484</ref>. It consists of a disulfide-linked homodimer, with each subunit containing 638 residues. Each subunit also contains a <scene name='Sandbox_Reserved_331/Copper_ligand/5'>copper ligand</scene> near the active site, which is coordinated by three histidine residues. Located near the Cu<sup>2+</sup> ligand is a tyrosine residue that has been modified into topa-quinone, which is also a cofactor in all other copper amine oxidases<ref name="Parsons">PMID:8591028</ref>. The active site of the enzyme is located near the center of the homodimer, which is connected to the outside of the enzyme by an extensively hydrated channel. It is suspected that the water helps to carry O<sub>2</sub> to the active site, as well as being used in the reaction itself<ref name="Mure">PMID:12135347</ref>.
<div style="clear:left;"></div>

== Reaction Mechanism ==
Copper amine oxidase catalyzes the oxidation of a primary amine to the corresponding aldehyde, yielding hydrogen peroxide and free ammonia. An example of this is the oxidation of [http://en.wikipedia.org/wiki/Tyramine tyramine]:

[[Image:Tyramine oxidation.png|thumb|center|600px|The oxidation of tyramine, yielding the corresponding aldehyde, hydrogen peroxide, and ammonia.]]
<div style="clear:left;"></div>

=== Reductive half-reaction ===
In the reductive half-reaction, the carbonyl of topa-quinone reacts with the primary amine of the substrate, forming the substrate Schiff-base intermediate ([http://www.proteopedia.org/wiki/index.php/2cwv 2cwv]). The α-proton is then abstracted by a conserved aspartic acid residue (Asp298), which forms the product Schiff-base intermediate ([http://www.proteopedia.org/wiki/index.php/2cwv 2cwv]). Several studies have shown that the abstraction of the α-proton proceeds through [http://en.wikipedia.org/wiki/Quantum_tunnelling quantum-mechanical tunneling], which allows the proton to pass through an energy barrier which it would otherwise not be able to pass according to classical mechanics<ref name="Murakawa" /><ref name="Grant">PMID:2790014</ref>.This bond is then hydrolyzed, which yields the aldehyde form of the substrate, the aminoquinol form of topa-quinone, and a proton.
[[Image:2d1wReductive Half.png|thumb|center|800px|The reductive half-reaction in the oxidation of a primary amine by copper amine oxidase.]]
<div style="clear:left;"></div>

=== Oxidative half-reaction ===
In the oxidative half-reaction, electrons are transferred from the reduced form of topa-quinone to O<sub>2</sub>, forming a superoxide ion that is stabilized by the Cu<sup>2+</sup> ligand. Reduction of the superoxide by the amino-quinone form of topa-quinone yields peroxide and the imino-quinone form, leading to the release of hydrogen peroxide. Hydrolysis of the imino-quinone form of topa-quinone then releases free ammonia, and regenerates the oxidized form of topa-quinone<ref name="Grant" />.
[[Image:2d1w Oxidative Half.png|thumb|center|800px|The oxidative half-reaction, in which topa-quinone is restored to its oxidized form, releasing ammonia and hydrogen peroxide.]]
<div style="clear:left;"></div>
= Additional Resources =
*[http://www.pdb.org/pdb/explore/explore.do?structureId=2D1W Entry 2D1W in the RCSB Protein Data Bank]
*[http://www.google.ca/url?sa=t&source=web&cd=2&ved=0CB8QFjAB&url=http%3A%2F%2Fwww.jbc.org%2Fcontent%2F271%2F9%2F4718.full.pdf&rct=j&q=Topa%20quinone&ei=lb6UTZyZH8PdiAKF9t39CA&usg=AFQjCNFe66G0M8KGm8HD9rmSgzSyZwi9RQ&sig2=nwPWJNlka1WrmFatRPFH9Q&cad=rja The Biosynthesis of Topa Quinone Cofactor in Bacterial Amine Oxidases]

= References =

<references />

Sandbox Reserved 331

2011-04-07T07:21:50Z

Raymond Lyle: Sandbox Reserved 331 moved to Copper Amine Oxidase

#REDIRECT [[Copper Amine Oxidase]]

Copper Amine Oxidase

2011-04-07T07:21:50Z

Raymond Lyle: Sandbox Reserved 331 moved to Copper Amine Oxidase

{{Template:Sandbox_Reserved_BCMB307}}

=Copper Amine Oxidase=
__TOC__
{{STRUCTURE_2d1w | PDB=2d1w | SCENE= }}
== Structure ==
[[Image:TTS.png|thumb|left|alt=3-((3E)-4-HYDROXY-3-{[2-(4-HYDROXYPHENYL)ETHYL]IMINO}-6-OXOCYCLOHEXA-1,4-DIEN-1-YL)ALANINE.|Residue 382 is a tyrosine residue, modified into topa-quinone, shown here bound to tyramine.]] 2d1w is the tyramine-bound substrate Schiff-base intermediate of [http://en.wikipedia.org/wiki/Amine_oxidase_%28copper-containing%29 copper amine oxidase] derived from [http://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis]. Copper amine oxidases are classified as EC 1.4.3.6 in the EC number classification system of enzymes, and they belong to the larger class of [http://en.wikipedia.org/wiki/Oxidoreductase oxidoreductases]. The structure of this enzyme was determined by Murakawa ''et al.'' in 2005, by x-ray diffraction<ref name="Murakawa">PMID:16487484</ref>. It consists of a disulfide-linked homodimer, with each subunit containing 638 residues. Each subunit also contains a <scene name='Sandbox_Reserved_331/Copper_ligand/5'>copper ligand</scene> near the active site, which is coordinated by three histidine residues. Located near the Cu<sup>2+</sup> ligand is a tyrosine residue that has been modified into topa-quinone, which is also a cofactor in all other copper amine oxidases<ref name="Parsons">PMID:8591028</ref>. The active site of the enzyme is located near the center of the homodimer, which is connected to the outside of the enzyme by an extensively hydrated channel. It is suspected that the water helps to carry O<sub>2</sub> to the active site, as well as being used in the reaction itself<ref name="Mure">PMID:12135347</ref>.
<div style="clear:left;"></div>

== Reaction Mechanism ==
Copper amine oxidase catalyzes the oxidation of a primary amine to the corresponding aldehyde, yielding hydrogen peroxide and free ammonia. An example of this is the oxidation of [http://en.wikipedia.org/wiki/Tyramine tyramine]:

[[Image:Tyramine oxidation.png|thumb|center|600px|The oxidation of tyramine, yielding the corresponding aldehyde, hydrogen peroxide, and ammonia.]]
<div style="clear:left;"></div>

=== Reductive half-reaction ===
In the reductive half-reaction, the carbonyl of topa-quinone reacts with the primary amine of the substrate, forming the substrate Schiff-base intermediate ([http://www.proteopedia.org/wiki/index.php/2cwv 2cwv]). The α-proton is then abstracted by a conserved aspartic acid residue (Asp298), which forms the product Schiff-base intermediate ([http://www.proteopedia.org/wiki/index.php/2cwv 2cwv]). Several studies have shown that the abstraction of the α-proton proceeds through [http://en.wikipedia.org/wiki/Quantum_tunnelling quantum-mechanical tunneling], which allows the proton to pass through an energy barrier which it would otherwise not be able to pass according to classical mechanics<ref name="Murakawa" /><ref name="Grant">PMID:2790014</ref>.This bond is then hydrolyzed, which yields the aldehyde form of the substrate, the aminoquinol form of topa-quinone, and a proton.
[[Image:2d1wReductive Half.png|thumb|center|800px|The reductive half-reaction in the oxidation of a primary amine by copper amine oxidase.]]
<div style="clear:left;"></div>

=== Oxidative half-reaction ===
In the oxidative half-reaction, electrons are transferred from the reduced form of topa-quinone to O<sub>2</sub>, forming a superoxide ion that is stabilized by the Cu<sup>2+</sup> ligand. Reduction of the superoxide by the amino-quinone form of topa-quinone yields peroxide and the imino-quinone form, leading to the release of hydrogen peroxide. Hydrolysis of the imino-quinone form of topa-quinone then releases free ammonia, and regenerates the oxidized form of topa-quinone<ref name="Grant" />.
[[Image:2d1w Oxidative Half.png|thumb|center|800px|The oxidative half-reaction, in which topa-quinone is restored to its oxidized form, releasing ammonia and hydrogen peroxide.]]
<div style="clear:left;"></div>
= Additional Resources =
*[http://www.pdb.org/pdb/explore/explore.do?structureId=2D1W Entry 2D1W in the RCSB Protein Data Bank]
*[http://www.google.ca/url?sa=t&source=web&cd=2&ved=0CB8QFjAB&url=http%3A%2F%2Fwww.jbc.org%2Fcontent%2F271%2F9%2F4718.full.pdf&rct=j&q=Topa%20quinone&ei=lb6UTZyZH8PdiAKF9t39CA&usg=AFQjCNFe66G0M8KGm8HD9rmSgzSyZwi9RQ&sig2=nwPWJNlka1WrmFatRPFH9Q&cad=rja The Biosynthesis of Topa Quinone Cofactor in Bacterial Amine Oxidases]

= References =

<references />

2011-03-13T02:43:48Z

Raymond Lyle: The oxidation of tyramine, a primary amine, to an aldehyde, as catalyzed by copper amine oxidase.

== Summary ==
The oxidation of tyramine, a primary amine, to an aldehyde, as catalyzed by copper amine oxidase.
== Licensing ==
{{PD-self}}

2011-03-12T20:12:56Z

Raymond Lyle:

File:TTS.png

2011-03-12T20:11:59Z

Raymond Lyle: Modified residue 3-((3E)-4-hydroxy-3-{[2-(4-hydroxyphenyl)ethyl]imino}-6-oxocyclohexa-1,4-dien-1-yl)alanine, found in structure 2d1w.

== Summary ==
Modified residue 3-((3E)-4-hydroxy-3-{[2-(4-hydroxyphenyl)ethyl]imino}-6-oxocyclohexa-1,4-dien-1-yl)alanine, found in structure 2d1w.
== Licensing ==
{{PD-self}}

Copper Amine Oxidase

2011-03-12T19:53:15Z

Raymond Lyle:

Copper Amine Oxidase

2011-03-12T19:52:28Z

Raymond Lyle:

Copper Amine Oxidase

2011-03-12T19:48:40Z

Raymond Lyle:

{{Template:Sandbox_Reserved_BCMB307}}

{{STRUCTURE_2d1w | PDB=2d1w | SCENE= }}

2d1w is a 2-chain copper amine oxidase from [http://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis].

== Structure ==

=== Ligand ===

A closeup of the Cu<sup>2+</sup> <scene name='Sandbox_Reserved_331/Copper_ligand/3'> ligand</scene>.

=== Modified Residue ===

== References ==

<references />

Copper Amine Oxidase

2011-03-12T19:37:59Z

Raymond Lyle:

{{Template:Sandbox_Reserved_BCMB307}}

{{STRUCTURE_2d1w | PDB=2d1w | SCENE= }}

2d1w is a 2-chain copper amine oxidase from [http://en.wikipedia.org/wiki/Arthrobacter_globiformis Arthrobacter globiformis].

== Structure ==

=== Ligand ===

A closeup of the Cu<sup>2+</sup> <scene name='Sandbox_Reserved_331/Copper_ligand/1'> ligand</scene>.

=== Modified Residue ===

== References ==

<references />