Glycosyltransferase Family 42 - Revision history

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

2021-12-18T21:16:30Z

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

Harry Brumer at 17:20, 23 September 2019

2019-09-23T17:20:23Z

Spencer Williams at 12:56, 23 September 2019

2019-09-23T12:56:25Z

Spencer Williams at 12:56, 23 September 2019

2019-09-23T12:56:08Z

Spencer Williams at 22:50, 17 September 2019

2019-09-17T22:50:28Z

Harry Brumer: fixed category tag ID

2019-09-17T16:50:55Z

fixed category tag ID

Spencer Williams at 12:44, 16 September 2019

2019-09-16T12:44:17Z

Spencer Williams at 12:42, 16 September 2019

2019-09-16T12:42:23Z

Spencer Williams at 12:40, 16 September 2019

2019-09-16T12:40:10Z

Harry Brumer: /* Acceptor specificities */ Changes section header to broader title, also now identical to GH pages

2017-09-14T20:54:47Z

Acceptor specificities: Changes section header to broader title, also now identical to GH pages

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

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 |-
 |'''Mechanism'''
-|Inverting. CMP-NeuAc α-2,3-sialyltransferase (EC 2.4.99.-); donor is CMP-β-Neu5Ac
+|Inverting. CMP-β-NeuAc α-2,3-sialyltransferase (EC 2.4.99.-)
 |-
 |'''Active site residues'''

@@ Line 48: / Line 48: @@
 == Family Firsts ==
 ;First catalytic residue identification: His188 is the catalytic base in the ''Campylobacter jejuni'' GT42 known as Cst-II <cite>Chan2009</cite>. His201 is the catalytic base in''Campylobacter jejuni'' Cst-II.
-;First substrate specficity determination: GT42 known as Cst-IThe CjGT-42 enzyme Cst-II from strain OH4384, was the demonstrated to be first sialyltransferase which could make both &alpha;2,3 and &alpha;2,8 linkages <cite>Gilbert2002</cite>.  This bi-functional activity is unique to GT-42.
+;First substrate specificity determination: GT42 known as Cst-IThe CjGT-42 enzyme Cst-II from strain OH4384, was the demonstrated to be first sialyltransferase which could make both &alpha;2,3 and &alpha;2,8 linkages <cite>Gilbert2002</cite>.  This bi-functional activity is unique to GT-42.
 ;First 3-D structure: The CjGT-42 enzymes Cst-I and Cst-II were the first sialyltransferases whose structure was determined by X-ray crystallography <cite>Chiu2004 Chiu2007</cite>.

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 |-
 |'''Active site residues'''
-|His188 is the catalytic base in the ''Campylobacter jejuni'' GT42 known as Cst-II
+|known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
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 == Substrate specificities ==
-The [[glycosyltransferases]] in GT-42 were originally examined from isolates of ''C. jejuni'' that express a number of ganglioside mimics, some of which have an α2,8-α2,3 linked di-sialic acid moiety <cite>Gilbert2008</cite>.  The CjGT-42 known as Cst-II was found as part of the lipooligosaccharide (LOS) biosynthesis operon <cite>Gilbert2000</cite>, which facilitated the correlation of gene content to LOS structure.  Based on the LOS structures which contained both α2,3 and α2,8 linked sialic acid it was predicted that there should be two sialyltransferases, but the surprising finding was that a single CjGT-42 enzyme, Cst-II, was making both linkages <cite>Gilbert2002</cite>.  This bi-functional enzyme has been shown to be a determinant in the development of post-infectious neuropathies (Guillain-Barré syndrome), due to an anti-ganglioside antibody response in some patients who were infected with ''C. jejuni'' <cite>Koga2005 vanBelkum2001</cite>.  Some species of ''Campylobacter'' express a second GT-42 enzyme known as Cst-I, which was in fact cloned first, but it has been shown not to be involved in LOS biosynthesis on the basis of gene knockouts in strains with both cst genes (Michel Gilbert, personal communication).  Cst-I contains an extended C-terminal domain of unknown function, and the target acceptor of this second CjGT-42 is not known at present.  The GT-42 family also contains members from ''H. influenzae'' and ''P. multocida'', in which the GT-42 enzymes are one of two or three resident sialyltransferases.  In ''H. influenzae'' the first GT-42 enzyme to be described was the α2,3-sialyltransferase Lic3A <cite>Hood2001</cite>, followed by a second a2,3/2,8-bi-functional version known as Lic3B <cite>Fox2006</cite>.  In ''H. influenzae'' the ''in vivo'' acceptor for Lic3A/B is the simple disaccharide lactose in contrast to the more complex ganglioside mimics seen in ''C. jejuni'' <cite>Schweda2007</cite>. At present there are uncharacterized members of GT42 from ''Helicobacter acinonychis'' str. Sheeba, ''H. mustelae'' that were identified through genome sequencing, but which have not been linked to specific sialylated structures.
+The [[glycosyltransferases]] in family GT42 were originally examined from isolates of ''C. jejuni'' that express a number of ganglioside mimics, some of which have an α2,8-α2,3 linked di-sialic acid moiety <cite>Gilbert2008</cite>.  The CjGT42 known as Cst-II was found as part of the lipooligosaccharide (LOS) biosynthesis operon <cite>Gilbert2000</cite>, which facilitated the correlation of gene content to LOS structure.  Based on the LOS structures which contained both α2,3 and α2,8 linked sialic acid it was predicted that there should be two sialyltransferases, but the surprising finding was that a single CjGT-42 enzyme, Cst-II, was making both linkages <cite>Gilbert2002</cite>.  This bi-functional enzyme has been shown to be a determinant in the development of post-infectious neuropathies (Guillain-Barré syndrome), due to an anti-ganglioside antibody response in some patients who were infected with ''C. jejuni'' <cite>Koga2005 vanBelkum2001</cite>.  Some species of ''Campylobacter'' express a second family GT42 enzyme known as Cst-I, which was in fact cloned first, but it has been shown not to be involved in LOS biosynthesis on the basis of gene knockouts in strains with both cst genes (Michel Gilbert, personal communication).  Cst-I contains an extended C-terminal domain of unknown function, and the target acceptor of this second CjGT-42 is not known at present.  The GT42 family also contains members from ''H. influenzae'' and ''P. multocida'', in which the GT42 enzymes are one of two or three resident sialyltransferases.  In ''H. influenzae'' the first GT-42 enzyme to be described was the α2,3-sialyltransferase Lic3A <cite>Hood2001</cite>, followed by a second a2,3/2,8-bi-functional version known as Lic3B <cite>Fox2006</cite>.  In ''H. influenzae'' the ''in vivo'' acceptor for Lic3A/B is the simple disaccharide lactose in contrast to the more complex ganglioside mimics seen in ''C. jejuni'' <cite>Schweda2007</cite>. At present there are uncharacterized members of GT42 from ''Helicobacter acinonychis'' str. Sheeba, ''H. mustelae'' that were identified through genome sequencing, but which have not been linked to specific sialylated structures.
 == Kinetics and Mechanism ==
@@ Line 36: / Line 35: @@
 == Catalytic Residues ==
-His188 in CjGT-42 Cst-II<sub>OH4383</sub> appears to be the catalytic [[general base]].  The amino acids Asn51 and Leu54 had the most effect on the bi-functional activity of Cst-II, but only Asn51 was shown to be critical for the α2,8-sialyltransferase activity in this variant of Cst-II. There are members of GT42 which have an Asn at an equivalent sequence position that are not bi-functional, but they have much lower overall sequence homolgy with Cst-II<sub>OH4384</sub>.
+His188 in CjGT42 Cst-II<sub>OH4383</sub> appears to be the catalytic [[general base]] <cite>Chan2009</cite>.  The amino acids Asn51 and Leu54 had the most effect on the bi-functional activity of Cst-II, but only Asn51 was shown to be critical for the α2,8-sialyltransferase activity in this variant of Cst-II. There are members of GT42 which have an Asn at an equivalent sequence position that are not bi-functional, but they have much lower overall sequence homolgy with Cst-II<sub>OH4384</sub>.
 == Three-dimensional structures ==
-The CjGT-42 enzymes Cst-I and Cst-II were the first sialyltransferases whose structure was determined by X-ray crystallography <cite>Chiu2004 Chiu2007</cite>, and they share the same basic structure.  GT-42 enzymes have a modified GT-A type fold characterized by a single &alpha;/&beta; Rossmann fold nucleotide binding domain, and a flexible lid domain composed of a coil and two helices.  Unlike the typical GT-A fold, CjGT-42 enzymes lack the conserved DXD motif and are metal-ion independent.  The enzyme structure revealed a tetramer in which each monomer carries an independent active site, and examination of the active site residues suggested a conserved histidine, His188 in Cst-II, as the catalytic base.
+The CjGT42 enzymes Cst-I and Cst-II were the first sialyltransferases whose 3D structure was determined by X-ray crystallography <cite>Chiu2004 Chiu2007</cite>, and they share the same basic structure.  GT42 enzymes have a modified GT-A type fold characterized by a single &alpha;/&beta; Rossmann fold nucleotide binding domain, and a flexible lid domain composed of a coil and two helices.  Unlike the typical GT-A fold, CjGT-42 enzymes lack the conserved DXD motif and are metal-ion independent.  The enzyme structure revealed a tetramer in which each monomer carries an independent active site, and examination of the active site residues suggested a conserved histidine, His188 in Cst-II, as the catalytic base.
 [[Glycosyltransferase]] structures often have a “lid” domain, which is a mobile loop that undergoes a conformational change upon binding a substrate <cite>Lairson2008</cite>.  The lid domain in Cst-I and Cst-II contains residues which interact with the donor and/or acceptor.  A common feature of transferase substrate binding is the role of aromatic residues stacking onto the base of the sugar-nucleotide.  In Cst-I the aromatic residue is Tyr171 and in Cst-II it is Tyr156, both of which are conserved in GT-42 and occur in the lid domain.  There is no structure of a ternary complex for GT-42 so it is not possible to know all of the interactions that are involved in substrate binding, but there are donor complexes with the incompetent donor CMP-3-fluoro-Neu5Ac and acceptor models have been examined to predict interactions <cite>Chiu2007</cite>.  In Cst-I, Phe190 appears to prevent sialylated acceptors from binding in the active site.  In Cst-II, this Phe residue is replaced by Ala175, which opens up a pocket for the carboxyl group of a modelled sialyl-lactose acceptor <cite>Chiu2007</cite>.
@@ Line 48: / Line 47: @@
 == Family Firsts ==
-The CjGT-42 enzyme Cst-II from strain OH4384, was the demonstrated to be first sialyltransferase which could make both &alpha;2,3 and &alpha;2,8 linkages <cite>Gilbert2002</cite>.  This bi-functional activity is unique to GT-42.
+;First catalytic residue identification: His188 is the catalytic base in the ''Campylobacter jejuni'' GT42 known as Cst-II <cite>Chan2009</cite>. His201 is the catalytic base in''Campylobacter jejuni'' Cst-II.
+;First substrate specficity determination: GT42 known as Cst-IThe CjGT-42 enzyme Cst-II from strain OH4384, was the demonstrated to be first sialyltransferase which could make both &alpha;2,3 and &alpha;2,8 linkages <cite>Gilbert2002</cite>.  This bi-functional activity is unique to GT-42.
-The CjGT-42 enzymes Cst-I and Cst-II were the first sialyltransferases whose structure was determined by X-ray crystallography <cite>Chiu2004 Chiu2007</cite>, and they share the same basic structure.  GT-42 enzymes have a modified GT-A type fold characterized by a single a/b Rossmann fold nucleotide binding domain, and a flexible lid domain composed of a coil and two helices.
+;First 3-D structure: The CjGT-42 enzymes Cst-I and Cst-II were the first sialyltransferases whose structure was determined by X-ray crystallography <cite>Chiu2004 Chiu2007</cite>.
 == References ==

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 |-
 |'''Mechanism'''
-|CMP-NeuAc α-2,3-sialyltransferase (EC 2.4.99.-) which is inverting, donor is CMP-β-Neu5Ac
+|Inverting. CMP-NeuAc α-2,3-sialyltransferase (EC 2.4.99.-); donor is CMP-β-Neu5Ac
 |-
 |'''Active site residues'''

← Older revision		Revision as of 16:50, 17 September 2019
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	</biblio>		</biblio>

−	[[Category:Glycosyltransferase Families\|~~GH042~~]]	+	[[Category:Glycosyltransferase Families\|GT042]]

← Older revision		Revision as of 20:54, 14 September 2017
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−	== ~~Acceptor~~ specificities ==	+	== Substrate specificities ==
	The [[glycosyltransferases]] in GT-42 were originally examined from isolates of ''C. jejuni'' that express a number of ganglioside mimics, some of which have an α2,8-α2,3 linked di-sialic acid moiety <cite>Gilbert2008</cite>. The CjGT-42 known as Cst-II was found as part of the lipooligosaccharide (LOS) biosynthesis operon <cite>Gilbert2000</cite>, which facilitated the correlation of gene content to LOS structure. Based on the LOS structures which contained both α2,3 and α2,8 linked sialic acid it was predicted that there should be two sialyltransferases, but the surprising finding was that a single CjGT-42 enzyme, Cst-II, was making both linkages <cite>Gilbert2002</cite>. This bi-functional enzyme has been shown to be a determinant in the development of post-infectious neuropathies (Guillain-Barré syndrome), due to an anti-ganglioside antibody response in some patients who were infected with ''C. jejuni'' <cite>Koga2005 vanBelkum2001</cite>. Some species of ''Campylobacter'' express a second GT-42 enzyme known as Cst-I, which was in fact cloned first, but it has been shown not to be involved in LOS biosynthesis on the basis of gene knockouts in strains with both cst genes (Michel Gilbert, personal communication). Cst-I contains an extended C-terminal domain of unknown function, and the target acceptor of this second CjGT-42 is not known at present. The GT-42 family also contains members from ''H. influenzae'' and ''P. multocida'', in which the GT-42 enzymes are one of two or three resident sialyltransferases. In ''H. influenzae'' the first GT-42 enzyme to be described was the α2,3-sialyltransferase Lic3A <cite>Hood2001</cite>, followed by a second a2,3/2,8-bi-functional version known as Lic3B <cite>Fox2006</cite>. In ''H. influenzae'' the ''in vivo'' acceptor for Lic3A/B is the simple disaccharide lactose in contrast to the more complex ganglioside mimics seen in ''C. jejuni'' <cite>Schweda2007</cite>. At present there are uncharacterized members of GT42 from ''Helicobacter acinonychis'' str. Sheeba, ''H. mustelae'' that were identified through genome sequencing, but which have not been linked to specific sialylated structures.		The [[glycosyltransferases]] in GT-42 were originally examined from isolates of ''C. jejuni'' that express a number of ganglioside mimics, some of which have an α2,8-α2,3 linked di-sialic acid moiety <cite>Gilbert2008</cite>. The CjGT-42 known as Cst-II was found as part of the lipooligosaccharide (LOS) biosynthesis operon <cite>Gilbert2000</cite>, which facilitated the correlation of gene content to LOS structure. Based on the LOS structures which contained both α2,3 and α2,8 linked sialic acid it was predicted that there should be two sialyltransferases, but the surprising finding was that a single CjGT-42 enzyme, Cst-II, was making both linkages <cite>Gilbert2002</cite>. This bi-functional enzyme has been shown to be a determinant in the development of post-infectious neuropathies (Guillain-Barré syndrome), due to an anti-ganglioside antibody response in some patients who were infected with ''C. jejuni'' <cite>Koga2005 vanBelkum2001</cite>. Some species of ''Campylobacter'' express a second GT-42 enzyme known as Cst-I, which was in fact cloned first, but it has been shown not to be involved in LOS biosynthesis on the basis of gene knockouts in strains with both cst genes (Michel Gilbert, personal communication). Cst-I contains an extended C-terminal domain of unknown function, and the target acceptor of this second CjGT-42 is not known at present. The GT-42 family also contains members from ''H. influenzae'' and ''P. multocida'', in which the GT-42 enzymes are one of two or three resident sialyltransferases. In ''H. influenzae'' the first GT-42 enzyme to be described was the α2,3-sialyltransferase Lic3A <cite>Hood2001</cite>, followed by a second a2,3/2,8-bi-functional version known as Lic3B <cite>Fox2006</cite>. In ''H. influenzae'' the ''in vivo'' acceptor for Lic3A/B is the simple disaccharide lactose in contrast to the more complex ganglioside mimics seen in ''C. jejuni'' <cite>Schweda2007</cite>. At present there are uncharacterized members of GT42 from ''Helicobacter acinonychis'' str. Sheeba, ''H. mustelae'' that were identified through genome sequencing, but which have not been linked to specific sialylated structures.