Phosphorylases - Revision history

Spencer Williams at 04:56, 12 September 2024

2024-09-12T04:56:10Z

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

2021-12-18T21:20:17Z

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

Spencer Williams: /* Retaining phosphorylase mechanism */

2017-03-10T05:37:45Z

Retaining phosphorylase mechanism

Spencer Williams: /* Retaining phosphorylase mechanism */

2017-03-10T05:37:08Z

Retaining phosphorylase mechanism

Spencer Williams: /* Retaining phosphorylase mechanism */

2017-03-06T22:24:34Z

Retaining phosphorylase mechanism

Spencer Williams: /* Retaining phosphorylase mechanism */

2017-03-06T21:45:46Z

Retaining phosphorylase mechanism

Spencer Williams: /* Examples */

2017-03-06T21:37:09Z

Examples

Spencer Williams at 00:47, 21 October 2013

2013-10-21T00:47:09Z

Harry Brumer: /* Examples */

2013-06-25T16:44:02Z

Examples

Spencer Williams at 04:09, 24 June 2013

2013-06-24T04:09:04Z

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 [[Image:Retaining&Inverting_phosphorylase.png|center|700px]]
-The energy content of the sugar 1-phosphate product means that the cleavage reaction is often in a practical sense reversible and, in Nature, these enzymes may be involved in either synthesis or cleavage of the glycosidic bond. As such there is a relatively fine distinction among sugar phosphorylases, [[glycoside hydrolase]]s and classical sugar nucleoside (di)phosphate dependent [[glycosyltransferase]]s. In the last case the synthetic reaction is normally, but not always, irreversible because of the higher energy of a sugar nucleoside (di)phosphate.
+The energy content of the sugar 1-phosphate product means that the cleavage reaction is often in a practical sense reversible and, in nature, these enzymes may be involved in either synthesis or cleavage of the glycosidic bond. As such there is a relatively fine distinction among sugar phosphorylases, [[glycoside hydrolase]]s and classical sugar nucleoside (di)phosphate dependent [[glycosyltransferase]]s. In the last case the synthetic reaction is normally, but not always, irreversible because of the higher energy of a sugar nucleoside (di)phosphate.
 <br>
 <br>
-The phosphorylases are classified into various [[glycoside hydrolase]] (GH) and [[glycosyltransferase]] (GT) families on the basis of sequence similarity <cite>Nakai2013</cite>. Glycoside phosphorylases have been found in a total of 7 GH and GT families (see below).
+The phosphorylases are classified into various [[glycoside hydrolase]] (GH) and [[glycosyltransferase]] (GT) families on the basis of sequence similarity <cite>Nakai2013</cite>. Glycoside phosphorylases have been found in more than 8 GH and GT families (see below).
 ===Glycosyltransferase-like phosphorylases===
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 *Family [[GT4]] contains trehalose phosphorylase, a retaining enzyme.
 *Family [[GT35]] contains glycogen and starch phosphorylases.
 ===Glycoside hydrolase-like phosphorylases===
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 ==Mechanism of glycosyltransferase-like phosphorylases==
-Only retaining enzymes have been identified within the currently known glycosyltransferase-like phosphorylases
+Both retaining ([[GT4]], [[GT35]]) and inverting ([[GT108]] enzymes have been identified within the glycosyltransferase-like phosphorylases
 ===Retaining phosphorylase mechanism===

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 {{CuratorApproved}}
-* [[Author]]s: ^^^Spencer Williams^^^, ^^^Motomitsu Kitaoka^^^
+* [[Author]]s: [[User:Spencer Williams|Spencer Williams]], [[User:Motomitsu Kitaoka|Motomitsu Kitaoka]]
-* [[Responsible Curator]]: ^^^Spencer Williams^^^
+* [[Responsible Curator]]: [[User:Spencer Williams|Spencer Williams]]
 ----
 ==Overview==

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 ===Retaining phosphorylase mechanism===
-Phosphorolysis of a glycoside with net retention of configuration by the GH-like retaining phosphorylases is achieved via two step, double-displacement mechanisms involving a nucleophilic participation and a covalent intermediate. The mechanism of these enzymes involves a covalent glycosyl-enzyme intermediate, as shown in the figure below. Reaction occurs with acid/base and nucleophilic assistance provided by two amino acid side chains, typically glutamate or aspartate, but occasionally histidine (for family [[GH3]]NagZ enzymes). In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is cleaved by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]]. An alternative mechanism for retention of anomeric configuration has been proposed involving direct front-side nucleophilic displacement (S<sub>N</sub>i). Both of these mechanisms bear considerable analogy to those proposed for retaining glycosyltransferases <cite>Lairsson2004 Lairsson2008 </cite>.
+Phosphorolysis of a glycoside with net retention of configuration by the GH-like retaining phosphorylases is achieved via two step, double-displacement mechanisms involving a nucleophilic participation and a covalent intermediate. The mechanism of these enzymes involves a covalent glycosyl-enzyme intermediate, as shown in the figure below. Reaction occurs with acid/base and nucleophilic assistance provided by two amino acid side chains, typically glutamate or aspartate, but occasionally histidine (for family [[GH3]] NagZ enzymes). In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is cleaved by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]]. An alternative mechanism for retention of anomeric configuration has been proposed involving direct front-side nucleophilic displacement (S<sub>N</sub>i). Both of these mechanisms bear considerable analogy to those proposed for retaining glycosyltransferases <cite>Lairsson2004 Lairsson2008 </cite>.
 [[Image:Retaining_a-glycoside_phosphorylase_mechanism.png|center|600px]]

@@ Line 47: / Line 47: @@
 ===Retaining phosphorylase mechanism===
-Phosphorolysis of a glycoside with net retention of configuration by the GH-like retaining phosphorylases is achieved via two step, double-displacement mechanisms involving a nucleophilic participation and a covalent intermediate. These broadly fall into two general types based on whether nucleophilic involves an enzymic residue, or a residue that forms part of the substrate. The first type of mechanism involves a covalent glycosyl-enzyme intermediate, as shown in the figure below. Reaction occurs with acid/base and nucleophilic assistance provided by two amino acid side chains, typically glutamate or aspartate. In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is cleaved by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]]. An alternative mechanism for retention of anomeric configuration has been proposed involving direct front-side nucleophilic displacement (S<sub>N</sub>i). Both of these mechanisms bear considerable analogy to those proposed for retaining glycosyltransferases <cite>Lairsson2004 Lairsson2008 </cite>.
+Phosphorolysis of a glycoside with net retention of configuration by the GH-like retaining phosphorylases is achieved via two step, double-displacement mechanisms involving a nucleophilic participation and a covalent intermediate. The mechanism of these enzymes involves a covalent glycosyl-enzyme intermediate, as shown in the figure below. Reaction occurs with acid/base and nucleophilic assistance provided by two amino acid side chains, typically glutamate or aspartate, but occasionally histidine (for family [[GH3]]NagZ enzymes). In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is cleaved by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]]. An alternative mechanism for retention of anomeric configuration has been proposed involving direct front-side nucleophilic displacement (S<sub>N</sub>i). Both of these mechanisms bear considerable analogy to those proposed for retaining glycosyltransferases <cite>Lairsson2004 Lairsson2008 </cite>.
 [[Image:Retaining_a-glycoside_phosphorylase_mechanism.png|center|600px]]
 ==Mechanism of glycosyltransferase-like phosphorylases==

@@ Line 47: / Line 47: @@
 ===Retaining phosphorylase mechanism===
-Phosphorolysis of a glycoside with net retention of configuration by the GH-like retaining phosphorylases is achieved via two step, double-displacement mechanisms involving a nucleophilic participation and a covalent intermediate. These broadly fall into two general types based on whether nucleophilic involves an enzymic residue, or a residue that forms part of the substrate. The first type of mechanism involves a covalent glycosyl-enzyme intermediate, as shown in the figure below. Reaction occurs with acid/base and nucleophilic assistance provided by two amino acid side chains, typically glutamate or aspartate. In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is hydrolyzed by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]]. An alternative mechanism for retention of anomeric configuration has been proposed involving direct front-side nucleophilic displacement (S<sub>N</sub>i). Both of these mechanisms bear considerable analogy to those proposed for retaining glycosyltransferases <cite>Lairsson2004 Lairsson2008 </cite>.
+Phosphorolysis of a glycoside with net retention of configuration by the GH-like retaining phosphorylases is achieved via two step, double-displacement mechanisms involving a nucleophilic participation and a covalent intermediate. These broadly fall into two general types based on whether nucleophilic involves an enzymic residue, or a residue that forms part of the substrate. The first type of mechanism involves a covalent glycosyl-enzyme intermediate, as shown in the figure below. Reaction occurs with acid/base and nucleophilic assistance provided by two amino acid side chains, typically glutamate or aspartate. In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is cleaved by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]]. An alternative mechanism for retention of anomeric configuration has been proposed involving direct front-side nucleophilic displacement (S<sub>N</sub>i). Both of these mechanisms bear considerable analogy to those proposed for retaining glycosyltransferases <cite>Lairsson2004 Lairsson2008 </cite>.
 [[Image:Retaining_a-glycoside_phosphorylase_mechanism.png|center|600px]]
-The second type of mechanism involves neighboring group participation and an oxazolinium ion intermediate, and occurs with ''N''-acetylhexosaminide phosphorylases, as shown in the figure below. The reaction involves the nucleophilic attack by the substrate 2-acetamide group, with [[general acid]] assistance provided by an amino acid side chain (histidine for family [[GH3]]NagZ enzymes). In the first step (called the glycosylation step), one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme [[intermediate]]. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves. In the second step (termed the deglycosylation step), the glycosyl enzyme is hydrolyzed by phosphate, with the other residue now acting as a base catalyst deprotonating the phosphate as it attacks. Each step passes through an [[oxocarbenium ion]]-like [[transition state]].
+The second type of mechanism involves neighboring group participation and an oxazolinium ion intermediate, and occurs with ''N''-acetylhexosaminide phosphorylases, as shown in the figure below. The reaction involves the nucleophilic attack by the substrate 2-acetamido group, with [[general acid]] assistance provided by an amino acid side chain (histidine for family [[GH3]]NagZ enzymes). This results in the formation of a [[oxazolinium ion]] [[intermediate]]. In the second step, the [[oxazolinium ion]] is opened by phosphate, reforming the 2-acetamido group and forming a glycosyl phosphate. In both steps an adjacent stablizing residue assists in stablizing the oxazolinium-ion [[oxocarbenium ion]]-like [[transition state]]s.
 ==Mechanism of glycosyltransferase-like phosphorylases==

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 ====Examples====
 *Family [[GH13]] contains sucrose phosphorylase and &alpha;-1,4-glucan:maltose 1-phosphate maltosyltransferase.
 *Family [[GH65]] contains maltose phosphorylase, trehalose phosphorylase, kojibiose (Glc-α-1,2-Glc) phosphorylase, nigerose (Glc-α-1,3-Glc) phosphorylase, and trehalose 6-phosphate phosphorylase.

@@ Line 29: / Line 29: @@
 *Family [[GH94]] contains cellobiose phosphorylase, cellodextrin phosphorylase, and chitobiose phosphorylase.
 *Family [[GH112]] contains β-galactoside phosphorylases such as β-1,3-D-galactosyl-D-hexososamine phosphorylase, and β-1,4-D-galactosyl-L-rhamnose phosphorylase.
-*Family [[GH130]] contains β-mannoside phosphorylases such as β-mannosyl-1,4-glucose phosphorylase and                     Normal  0          false  false  false    EN-US  JA  X-NONE                                                                                                                                                                                                                                                                                                                                                                     and β-1,4-mannooligosaccharide phosphorylase.
+*Family [[GH130]] contains β-mannoside phosphorylases such as β-mannosyl-1,4-glucose phosphorylase and β-1,4-mannooligosaccharide phosphorylase.
 ==Mechanism of glycoside hydrolase-like phosphorylases==