Glycoside Hydrolase Family 33 - Revision history

Harry Brumer: Finally updated to Curator Approved after a long period of inactivity - page is essentially complete

2023-01-05T00:59:26Z

Finally updated to Curator Approved after a long period of inactivity - page is essentially complete

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

2021-12-18T21:14:11Z

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

Harry Brumer: Added Friebolin1980 ref.

2020-06-23T21:26:00Z

Added Friebolin1980 ref.

Kyle Robinson at 17:48, 23 June 2020

2020-06-23T17:48:45Z

Kyle Robinson at 17:47, 23 June 2020

2020-06-23T17:47:55Z

Kyle Robinson at 17:46, 23 June 2020

2020-06-23T17:46:02Z

Steve Withers at 17:13, 23 June 2020

2020-06-23T17:13:49Z

Kyle Robinson at 16:48, 23 June 2020

2020-06-23T16:48:43Z

Kyle Robinson at 16:44, 23 June 2020

2020-06-23T16:44:24Z

Kyle Robinson at 16:39, 23 June 2020

2020-06-23T16:39:35Z

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
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 * [[Author]]: [[User:Kyle Robinson|Kyle Robinson]] and [[User:Junho Lee|Junho Lee]]
 * [[Responsible Curator]]:  [[User:Steve Withers|Steve Withers]]

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{UnderConstruction}}
-* [[Author]]: ^^^Kyle Robinson^^^ and ^^^Junho Lee^^^
+* [[Author]]: [[User:Kyle Robinson|Kyle Robinson]] and [[User:Junho Lee|Junho Lee]]
-* [[Responsible Curator]]:  ^^^Steve Withers^^^
+* [[Responsible Curator]]:  [[User:Steve Withers|Steve Withers]]
 ----

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 == Kinetics and Mechanism ==
-GH33 sialidases and trans-sialidases hydrolyse, or transfer sialic acids to acceptor sugars, with retention of anomeric configuration <cite> Friebolin1981</cite>. The general mechanism is depicted [[Glycoside_hydrolases#Alternative_nucleophiles|here]]. Considerable debate had occurred over whether an ionic or covalent intermediate was formed. However, a covalent glycosyl-enzyme intermediate was observed on ''T. cruzi'' trans-sialidase(TcTS) by mass spectrometry using a fluorinated sialic acid analogue and the labelled amino acid residue identified as Tyr342 by peptide mapping. Subsequent crystal structures provided further insight into the mechanism of the protozoan sialidase <cite> Amaya2004 Watts2003</cite>. Kinetic analysis of TcTS confirmed the expected ping-pong double-displacement mechanism, and a covalent intermediate was demonstrated, without use of a fluorinated derivative, by use of mass spectrometry <cite> Damager2008</cite>. Subsequent structural studies of two strictly hydrolytic sialidases from ''T. rangelli'' <cite> Watts2006</cite> and ''C. perfringens'' <cite> Newstead2008</cite> also characterised their covalent intermediates.
+GH33 sialidases and trans-sialidases hydrolyse, or transfer sialic acids to acceptor sugars, with retention of anomeric configuration <cite> Friebolin1980 Friebolin1981</cite>. The general mechanism is depicted [[Glycoside_hydrolases#Alternative_nucleophiles|here]]. Considerable debate had occurred over whether an ionic or covalent intermediate was formed. However, a covalent glycosyl-enzyme intermediate was observed on ''T. cruzi'' trans-sialidase(TcTS) by mass spectrometry using a fluorinated sialic acid analogue and the labelled amino acid residue identified as Tyr342 by peptide mapping. Subsequent crystal structures provided further insight into the mechanism of the protozoan sialidase <cite> Amaya2004 Watts2003</cite>. Kinetic analysis of TcTS confirmed the expected ping-pong double-displacement mechanism, and a covalent intermediate was demonstrated, without use of a fluorinated derivative, by use of mass spectrometry <cite> Damager2008</cite>. Subsequent structural studies of two strictly hydrolytic sialidases from ''T. rangelli'' <cite> Watts2006</cite> and ''C. perfringens'' <cite> Newstead2008</cite> also characterised their covalent intermediates.
 == Catalytic Residues ==
 ===Nucleophile===
 ===Acid Base Catalyst===
 The third mechanistically relevant conserved residue in the active site is Asp59, which serves as the acid/base catalyst, protonating the glycosidic oxygen as bond cleavage occurs. Following formation of the intermediate, Asp59 then serves as a base catalyst, activating the incoming water molecule (for simple hydrolytic pathways) or glycosyl acceptor (in the case of trans-sialidases) towards trans-glycosylation of the glycosyl-enzyme intermediate. This second attack leads to a double inversion at the anomeric center and a net retention of stereochemistry observed in the released product, Neu5Ac <cite> Amaya2004 Newstead2008 Damager2008 </cite>.
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 == Family Firsts ==
-;First stereochemistry determination: First determined by proton NMR by Friebolin et al <cite> Friebolin1981 </cite>.
+;First stereochemistry determination: First determined by proton NMR by Friebolin et al <cite>Friebolin1980 Friebolin1981</cite>.
 ;First catalytic nucleophile identification: NMR structures of Crennell and others were strongly suggestive, but mechanism was not clear. First definitively shown for the ''T. cruzi'' trans-sialidase by Watts et al through peptide mapping after labelling with 2,3-difluorosialic acid. <cite> Watts2003 </cite>.
 ;First general acid/base residue identification: Identified by X-ray crystallography by Crennell et al <cite> Crennell1993 </cite>.
@@ Line 70: / Line 70: @@
 #Moustafa2004 pmid=15226294
 #Watson2005 pmid=16206228
 #Gaskell1995 pmid=8591030
 #Friebolin1981 Friebolin, H. et al (1981) 1H-NMR Spectroscopic evidence for the release of N-acetyl-alpha-D-neuraminic acid as the first product of sialidase action. Biochem. Int. 3, 321-326.
+#Friebolin1980 pmid=6253376
 #Crennell1993 pmid=8234325
 #Tailford2015 pmid=26154892
 #Li1990 pmid=2254319
 #ChanBennet2012 pmid=22133027
 #WatsonBennet2004 pmid=15527797

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 == Three-dimensional structures ==
-All members of the sialidase superfamily, including the members of GH34 and GH83, display a 6 bladed beta-propeller sheet catalytic domain <cite> Amaya2004</cite>, which is accepted as the canonical neuraminidase fold.  The catalytic site structure is strictly conserved in all three families and contains an arginine triad which binds to the carboxylate in the C1 position of the sialic acid, a Tyr/Glu nucleophilic pair, and an aspartic acid that acts as the acid/base catalyst <cite> Buschiazzo2008</cite>.
+All members of the sialidase superfamily, including the members of [[GH34]] and [[GH83]], display a 6 bladed beta-propeller sheet catalytic domain <cite> Amaya2004</cite>, which is accepted as the canonical neuraminidase fold.  The catalytic site structure is strictly conserved in all three families and contains an arginine triad which binds to the carboxylate in the C1 position of the sialic acid, a Tyr/Glu nucleophilic pair, and an aspartic acid that acts as the acid/base catalyst <cite> Buschiazzo2008</cite>.
 Bacterial sialidases may also contain a membrane binding domain, signal domain and a lectin-like domain. Although not all bacterial sialidases have a lectin domain, the lectin domain can be used to recognize the sialic acid in certain species, such as ''V. cholerae'' <cite> Moustafa2004</cite>. Also it is not uncommon for a bacterial sialidase to have a carbohydrate binding module (CBM) as one of its domains, such as in ''M. viridifaciens'' sialidase  <cite> Gaskell1995 Watson2005 </cite>.

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 ===Nucleophile===
-The catalytic machinery is conserved throughout this family and, as shown by studies on TcTS, three key residues are involved: E230, Y342, D59. Since Watts first trapped the covalent 3F-sialyl enzyme intermediate on Tyr342 in 2003, many confirmatory structures have been solved. It is likely that tyrosine has evolved as the catalytic nucleophile, rather than the carboxylate moiety found in most retaining glycosidases, in order to minimize repulsive charge-charge interactions with the C-1 carboxylate of the sialic acids. The neutral tyrosine can more readily approach the anomeric centre, and is rendered more nucleophilic by an invariant glutamate, Glu230 for TcTS, that serves as a base catalyst for deprotonation/reprotonation of the tyrosine hydroxyl. See Chan et al <cite> ChanBennet2012 </cite> for a detailed analysis of the role of this residue in the GH33 sialidase from ''M. viridifaciens''.
+The catalytic machinery is conserved throughout this family and, as shown by studies on TcTS, three key residues are involved: Glu230, Tyr342, Asp59. Since Watts first trapped the covalent 3F-sialyl enzyme intermediate on Tyr342 in 2003, many confirmatory structures have been solved. It is likely that tyrosine has evolved as the catalytic nucleophile, rather than the carboxylate moiety found in most retaining glycosidases, in order to minimize repulsive charge-charge interactions with the C1 carboxylate of the sialic acids. The neutral tyrosine can more readily approach the anomeric centre, and is rendered more nucleophilic by an invariant glutamate, Glu230 for TcTS, that serves as a base catalyst for deprotonation/reprotonation of the tyrosine hydroxyl. See Chan et al <cite> ChanBennet2012 </cite> for a detailed analysis of the role of this residue in the GH33 sialidase from ''M. viridifaciens''.
 ===Acid Base Catalyst===
 The third mechanistically relevant conserved residue in the active site is Asp59, which serves as the acid/base catalyst, protonating the glycosidic oxygen as bond cleavage occurs. Following formation of the intermediate, Asp59 then serves as a base catalyst, activating the incoming water molecule (for simple hydrolytic pathways) or glycosyl acceptor (in the case of trans-sialidases) towards trans-glycosylation of the glycosyl-enzyme intermediate. This second attack leads to a double inversion at the anomeric center and a net retention of stereochemistry observed in the released product, Neu5Ac <cite> Amaya2004 Newstead2008 Damager2008 </cite>.

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 #ChanBennet2012 pmid=22133027
-#WatsonBennet2004 pmid15527797
+#WatsonBennet2004 pmid=15527797
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH033]]