Auxiliary Activity Family 11 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:14:46Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Harry Brumer at 17:34, 4 November 2019

2019-11-04T17:34:33Z

Harry Brumer: /* Kinetics and Mechanism */

2014-02-06T18:16:05Z

Kinetics and Mechanism

Harry Brumer at 18:14, 6 February 2014

2014-02-06T18:14:53Z

Gideon Davies at 10:49, 6 February 2014

2014-02-06T10:49:21Z

Glyn Hemsworth at 20:32, 5 February 2014

2014-02-05T20:32:02Z

Glyn Hemsworth at 16:52, 20 January 2014

2014-01-20T16:52:30Z

Glyn Hemsworth at 16:48, 20 January 2014

2014-01-20T16:48:47Z

Glyn Hemsworth at 16:43, 20 January 2014

2014-01-20T16:43:32Z

Glyn Hemsworth at 14:51, 20 January 2014

2014-01-20T14:51:28Z

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Glyn Hemsworth^^^
+* [[Author]]: [[User:Glyn Hemsworth|Glyn Hemsworth]]
-* [[Responsible Curator]]:  ^^^Gideon Davies^^^
+* [[Responsible Curator]]:  [[User:Gideon Davies|Gideon Davies]]
 ----

← Older revision		Revision as of 17:34, 4 November 2019
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	</biblio>		</biblio>

−	[[Category:Auxiliary Activity Families\|~~AA11~~]]	+	[[Category:Auxiliary Activity Families\|AA011]]

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 == Kinetics and Mechanism ==
-AA11s, like [[AA9]]s and [[AA10]]s, are copper dependent mono-oxygenases but the chemical mechanism by which these enzymes perform the reaction is yet to be elucidated. Recent quantum mechanical simulations suggest that [[AA9]]s are likely to oxidise cellulose using  a copper-oxyl, oxygen rebound mechanism <cite>Kim2013</cite> but further work is needed in this area. The differences in the copper coordination geometries between the families might further hint that they might use different mechanisms (Reviewed in <cite>Hemsworth2013c</cite>). As is the case for [[AA10]]s, the natural electron donor for AA11s is unknown, with no equivalent of cellobiose dehydrogenase yet discovered that is active on chitobiose. It is also unknown whether the N-terminal histidine in AA11s is N-methylated (as the enzyme in the published study was expressed in ''E. coli'' and not a filamentous fungi)as is seen in [[AA9]]s and what effect this will have on the reaction performed by the enzyme.
+AA11s, like [[AA9]]s and [[AA10]]s, are copper dependent mono-oxygenases but the chemical mechanism by which these enzymes perform the reaction is yet to be elucidated. Recent quantum mechanical simulations suggest that [[AA9]]s are likely to oxidise cellulose using  a copper-oxyl, oxygen rebound mechanism <cite>Kim2013</cite> but further work is needed in this area. The differences in the copper coordination geometries between the families might further hint that they might use different mechanisms (Reviewed in <cite>Hemsworth2013c</cite>). As is the case for [[AA10]]s, the natural electron donor for AA11s is unknown, with no equivalent of cellobiose dehydrogenase yet discovered that is active on chitobiose. It is also unknown whether the N-terminal histidine in AA11s is N-methylated (as the enzyme in the published study was expressed in ''E. coli'' and not a filamentous fungi) as is seen in [[AA9]]s and what effect this will have on the reaction performed by the enzyme.
 == Catalytic Residues ==

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 The AA11 family of Lytic Polysaccharide Mono-oxygenases (LPMOs; first described in <cite>Eijsink2010</cite>) was identified using a bioinformatic 'module walking' approach <cite>Hemsworth2013</cite>. Many [[AA9]] proteins have C-terminal domains, which are often cellulose binding CBMs (eg. [[CBM1]]), but some have no known function (also see <cite>Horn2012</cite>). Sequence searches using one of these domains (termed X278) returned hits where the domain was fused with [[GH18]] family members and another set of domains of unknown function. Closer examination of these domains revealed that they had a likely signal peptide followed by a histidine, typical of LPMOs, though they otherwise lacked significant sequence similarity to either [[AA9]] or [[AA10]] family members.
-The only AA11 to be isolated to to date is from ''Aspergillus oryzae'' which showed copper dependent oxidase activity on chitin in the presence of ascorbate. The observed products were a mixture of mainly aldonic acids and unmodified oligosaccharides with a small amount of a -2Da species, which may be C4 oxidation or the C1 lactone prior to ring opening.  It is unknown at this stage whether AA11 family members will show any activity towards other substrates, whether they oxidise at positions other than C1 on the sugar ring or what the role of the X278 domain often found at the C-terminus is (although a chitin binding function would seem logical given its presence on GH18 chitinases and AA11).
+The only AA11 to be isolated to to date is from ''Aspergillus oryzae'' which showed copper dependent oxidase activity on chitin in the presence of ascorbate. The observed products were a mixture of mainly aldonic acids and unmodified oligosaccharides with a small amount of a -2Da species, which may be C4 oxidation or the C1 lactone prior to ring opening.  It is unknown at this stage whether AA11 family members will show any activity towards other substrates, whether they oxidise at positions other than C1 on the sugar ring or what the role of the X278 domain often found at the C-terminus is (although a chitin binding function would seem logical given its presence on [[GH18]] chitinases and AA11).
 == Kinetics and Mechanism ==

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
-{{UnderConstruction}}
+{{CuratorApproved}}
-* [[Author]]: ^^^Gideon Davies^^^ & ^^^Glyn Hemsworth^^^
+* [[Author]]: ^^^Glyn Hemsworth^^^
 * [[Responsible Curator]]:  ^^^Gideon Davies^^^
 ----
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 == Substrate specificities ==
-The AA11 family of Lytic Polysaccharide Mono-oxygenases (LPMOs) was identified using a bioinformatic 'module walking' approach <cite>Hemsworth2013</cite>. Many [[AA9]] proteins have C-terminal domains, which are often cellulose binding CBMs (eg. [[CBM1]]), but some have no known function (also see <cite>Horn2012</cite>). Sequence searches using one of these domains (termed X278) returned hits where the domain was fused with [[GH18]] family members and another set of domains of unknown function. Closer examination of these domains revealed that they had a likely signal peptide followed by a histidine, typical of LPMOs, though they otherwise lacked significant sequence similarity to either [[AA9]] or [[AA10]] family members.
+The AA11 family of Lytic Polysaccharide Mono-oxygenases (LPMOs; first described in <cite>Eijsink2010</cite>) was identified using a bioinformatic 'module walking' approach <cite>Hemsworth2013</cite>. Many [[AA9]] proteins have C-terminal domains, which are often cellulose binding CBMs (eg. [[CBM1]]), but some have no known function (also see <cite>Horn2012</cite>). Sequence searches using one of these domains (termed X278) returned hits where the domain was fused with [[GH18]] family members and another set of domains of unknown function. Closer examination of these domains revealed that they had a likely signal peptide followed by a histidine, typical of LPMOs, though they otherwise lacked significant sequence similarity to either [[AA9]] or [[AA10]] family members.
-The only AA11 to be isolated to to date is from ''Aspergillus oryzae'' which showed copper dependent oxidase activity on chitin in the presence of ascorbate. The observed products were a mixture of mainly aldonic acids and unmodified oligosaccharides with a small amount of a -2Da species, which may be C4 oxidation or the C1 lactone prior to ring opening.  It is unknown at this stage whether AA11 family members will show any activity towards other substrates, whether they oxidise at positions other than C1 on the sugar ring or what the role of the X278 domain often found at the C-terminus is.
+The only AA11 to be isolated to to date is from ''Aspergillus oryzae'' which showed copper dependent oxidase activity on chitin in the presence of ascorbate. The observed products were a mixture of mainly aldonic acids and unmodified oligosaccharides with a small amount of a -2Da species, which may be C4 oxidation or the C1 lactone prior to ring opening.  It is unknown at this stage whether AA11 family members will show any activity towards other substrates, whether they oxidise at positions other than C1 on the sugar ring or what the role of the X278 domain often found at the C-terminus is (although a chitin binding function would seem logical given its presence on GH18 chitinases and AA11).
 == Kinetics and Mechanism ==
-AA11s, like [[AA9]]s and [[AA10]]s, are copper dependent mono-oxygenases but the chemical mechanism by which these enzymes perform the reaction is yet to be elucidated. Recent quantum mechanical simulations suggest that [[AA9]]s are likely to oxidise cellulose using  a copper-oxyl, oxygen rebound mechanism <cite>Kim2013</cite> but further work is needed in this area. The differences in the copper coordination geometries between the families might further hint that they might use different mechanisms (Reviewed in <cite>Hemsworth2013c</cite>). As is the case for [[AA10]]s, the natural electron donor for AA11s is unknown, with no equivalent of cellobiose dehydrogenase yet discovered that is active on chitobiose. It is also unknown whether the N-terminal histidine in AA11s is N-methylated as is seen in [[AA9]]s and what effect this will have on the reaction performed by the enzyme.
+AA11s, like [[AA9]]s and [[AA10]]s, are copper dependent mono-oxygenases but the chemical mechanism by which these enzymes perform the reaction is yet to be elucidated. Recent quantum mechanical simulations suggest that [[AA9]]s are likely to oxidise cellulose using  a copper-oxyl, oxygen rebound mechanism <cite>Kim2013</cite> but further work is needed in this area. The differences in the copper coordination geometries between the families might further hint that they might use different mechanisms (Reviewed in <cite>Hemsworth2013c</cite>). As is the case for [[AA10]]s, the natural electron donor for AA11s is unknown, with no equivalent of cellobiose dehydrogenase yet discovered that is active on chitobiose. It is also unknown whether the N-terminal histidine in AA11s is N-methylated (as the enzyme in the published study was expressed in ''E. coli'' and not a filamentous fungi)as is seen in [[AA9]]s and what effect this will have on the reaction performed by the enzyme.
 == Catalytic Residues ==
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 == References ==
 <biblio>
 #Hemsworth2013 pmid=24362702
 #Horn2012 pmid=22747961

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 == Family Firsts ==
 ;First family member identified: AA11 from ''A. oryzae'' <cite>Hemsworth2013</cite>.
-;First demonstration of oxidative cleavage: AoAA11 was shown to oxidatively cleave squid pen chitin producing a mixture of aldonic acids, unmodified oligonucleotides and undistinguishable lactone/C4 oxidation products <cite>Hemsworth2013</cite>.
+;First demonstration of oxidative cleavage: ''Ao''AA11 was shown to oxidatively cleave squid pen chitin producing a mixture of aldonic acids, unmodified oligosaccharides and undistinguishable lactone/C4 oxidation products <cite>Hemsworth2013</cite>.
 ;First 3-D structure: AA11 from ''A. oryzae'' with Zn2+ [{{PDBlink}}4mah 4MAH] & Cu(I)  [{{PDBlink}}4mai 4MAI] <cite>Hemsworth2013</cite>

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 == Catalytic Residues ==
-Like [[AA9]] and [[AA10]], AA11 utilises copper, which it binds through the "histidine brace" consisting of the N-terminal histidine's amino and imidazole groups together with the imidazole sidechain of another histidine. It is unknown at this stage whether AA11s possess the methylated N-terminal histidine observed in [[AA9]]s as the protein was produced recombinantly in ''E. coli''  which does not carry out this modification. Like [[AA9]], a tyrosine sidechain is in close proximity to the copper ion but it does not directly coordinate the metal in this case. [[AA9]]s typically leave the opposite side to the tyrosine open to solvent where water molecules are observed coordinating the metal ion <cite>Harris2010 Karkehabadi2008 Li2012 Quinlan2011</cite>. In [[AA10]]s there is an alanine in this position, which causes a distortion in the copper coordination geometry away from octahedral <cite>Hemsworth2013b</cite>. Interestingly AA11 has an alanine in a very similar position giving an active site structure somewhere between that of [[AA9]]s and [[AA10]]s. The structure was only determined with Cu(I) in the active site so the coordination geometry of Cu(II) was not directly observed but electron paramagnetic resonance spectroscopy confirmed that the copper coordination geometry lies somewhere between that of [[AA9]]s and [[AA10]]s <cite>Hemsworth2013</cite>.
+Like [[AA9]] and [[AA10]], AA11 utilises copper, which it binds through the "histidine brace" consisting of the N-terminal histidine's amino and imidazole groups together with the imidazole sidechain of another histidine. It is unknown at this stage whether AA11s possess the methylated N-terminal histidine observed in [[AA9]]s as the protein was produced recombinantly in ''E. coli''  which does not carry out this modification. Like [[AA9]], a tyrosine sidechain is in close proximity to the copper ion but it does not directly coordinate the metal in this case. [[AA9]]s typically leave the opposite side to the tyrosine open to solvent where water molecules are observed coordinating the metal ion <cite>Harris2010 Karkehabadi2008 Li2012 Quinlan2011</cite>. In [[AA10]]s there is an alanine in this position, which causes a distortion in the copper coordination geometry away from octahedral <cite>Hemsworth2013b Vaaje-Kolstad2012 Vaaje-Kolstad2005 Aachmann2012</cite>. Interestingly AA11 has an alanine in a very similar position giving an active site structure somewhere between that of [[AA9]]s and [[AA10]]s. The structure was only determined with Cu(I) in the active site so the coordination geometry of Cu(II) was not directly observed but electron paramagnetic resonance spectroscopy confirmed that the copper coordination geometry lies somewhere between that of [[AA9]]s and [[AA10]]s <cite>Hemsworth2013</cite>.
 == Three-dimensional structures ==
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 #Aachmann2012 pmid=23112164
 #Vaaje-Kolstad2012 pmid=22210154
 </biblio>
 [[Category:Auxiliary Activity Families|AA11]]