Difference between revisions of "Glycoside Hydrolase Family 33"

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Author: ^^^Tom Wennekes^^^
Responsible Curator: ^^^Steve Withers^^^

Glycoside Hydrolase Family GH33
Clan	GH-x
Mechanism	retaining/inverting
Active site residues	known/not known
CAZy DB link
https://www.cazy.org/GH33.html

Substrate specificities

Sialic acids, often known as N-acetylneuraminic acid (Neu5Ac, NANA, NeuNAc, NeuNA), are a family of nine carbon monosaccharides with a carboxylate group in the carbon 1 position that occupy the terminal position of the glycans, glycoproteins, glycolipids, and polysaccharides in cells and play important roles in interactions of the cell with its environment [1]. More than 50 sialic acid derivatives have been detected in eukaryotic and prokaryotic species; the most frequently detected sialic acids have an α(2,3) or α(2,6) linkage to galactose, N-acetylgalactosamine, and N-acetylglucosamine or an α(2,8) linkage to another sialic acids [2, 3, 4]. Sialic acids are hydrolyzed by sialidases (E.C. 3.2.1.18), and these enzymes are categorized into four different glycoside hydrolase(GH) families: GH33, GH34, and GH83 families are exosialidases while GH53 is an endosialidase [5].

GH33 includes most bacterial and simple eukaryotic sialidases and trans-sialidases [6]. Members of GH33 exhibit different preferences for the three most common sialic acid linkage types listed above, despite similar protein structure. For example, sialidases from Salmonella typhimurium LT2, Vibrio Cholerae, and Clostridium septicum, Clostridium sordellii, Clostridium chauvoei, Clostridium tertium demonstrate a higher hydrolysis activity towards α(2,3) linked substrates than α(2,6) linked substrates, while sialidases from Corynebacteriumm diphtheria and Micromonospora viridifaciens prefer to hydrolyze substrates with α(2,6) linkages [2]. One organism may produce sialidase isoenzymes with different substrate preferences. Pasteurella multocida produces two sialidases with different substrate preferences: NanH, an extracellular enzyme favouring α(2,3)-linked sialyllactose over α(2,6)-linked sialyllactose and NanB, a membrane bound enzyme that prefers α(2,6)-linked substrates over α(2,3)-linked substrates cite> Mizan2000. Similarly, membrane-bound NanA of Salmonella pneumoniae displays similar hydrolysis rates for sialyllactoses with α(2,3)-, α(2,6)- and α(2,8)-linkages whereas extracellular NanB from the same organism prefers α(2,3) linkage over substrates with the other two linkage types [2].

Kinetics and Mechanism

Sialidases and trans-sialidases hydrolyse or transfer sialic acids with retention of the anomeric configuration. Considerable debate had occurred over whether an ionic or covalent intermediate was formed. However, a glycosyl-enzyme intermediate was observed on T. cruzi trans-sialidase(TcTS) by mass spectrometry using a fluorinated sialic acid analogue, and a crystal structure determined [6, 7] Kinetic analysis of TcTS revealed a ping-pong double-displacement mechanism, and a covalent intermediate was demonstrated, without use of a fluorinated derivative, by use of mass spectrometry [8]. Subsequent structural studies of two strictly hydrolytic sialidases from T. rangelli [9] and Clostridium perfringens [10] also characterised their covalent intermediates.

Catalytic Residues

Content is to be added here.

Three-dimensional structures

Content is to be added here.

Family Firsts

First stereochemistry determination: Cite some reference here, with a short (1-2 sentence) explanation [11].
First catalytic nucleophile identification: Cite some reference here, with a short (1-2 sentence) explanation [12].
First general acid/base residue identification: Cite some reference here, with a short (1-2 sentence) explanation [13].
First 3-D structure: Cite some reference here, with a short (1-2 sentence) explanation [14].

References

All Medline abstracts: PubMed

@@ Line 31: / Line 31: @@
 Sialic acids, often known as ''N''-acetylneuraminic acid (Neu5Ac, NANA, NeuNAc, NeuNA), are a family of nine carbon monosaccharides with a carboxylate group in the carbon 1 position that occupy the terminal position of the glycans, glycoproteins, glycolipids, and polysaccharides in cells and play important roles in interactions of the cell with its environment <cite>Varki1997</cite>. More than 50 sialic acid derivatives have been detected in eukaryotic and prokaryotic species; the most frequently detected sialic acids have an  α(2,3) or α(2,6) linkage to galactose, ''N''-acetylgalactosamine, and ''N''-acetylglucosamine or an α(2,8) linkage to another sialic acids <cite>Kim2011 Varki2007 Vimir2004</cite>. Sialic acids are hydrolyzed by sialidases (E.C. 3.2.1.18), and these enzymes are categorized into four different glycoside hydrolase(GH) families: GH33, [[GH34]], and [[GH83]] families are exosialidases while [[GH53]] is an endosialidase <cite>Buschiazzo2008</cite>.
-GH33 includes most bacterial and simple eukaryotic sialidases and trans-sialidases <cite> Amaya2004</cite>. Members of GH33 exhibit different preferences for the three most common sialic acid linkage types listed above, despite similar protein structure. For example, sialidases from Salmonella typhimurium LT2, Vibrio Cholerae,  and Clostridium septicum, Clostridium sordellii, Clostridium chauvoei, Clostridium tertium  demonstrate a higher hydrolysis activity towards α(2,3) linked substrates than α(2,6) linked substrates, while sialidases from Corynebacteriumm diphtheria and Micromonospora viridifaciens prefer to hydrolyze substrates with α(2,6) linkages [2]. One organism may produce sialidase isoenzymes with different substrate preferences. Pasteurella multocida produces two sialidases with different substrate preferences: NanH, an extracellular enzyme favouring α(2,3)-linked sialyllactose over α(2,6)-linked sialyllactose and NanB, a membrane bound enzyme that prefers α(2,6)-linked substrates over α(2,3)-linked substrates  CITATION Miz \l 1042 [7]. Similarly, membrane-bound NanA of Salmonella pneumoniae  displays similar hydrolysis rates for sialyllactoses with α(2,3)-, α(2,6)- and α(2,8)-linkages whereas  extracellular NanB from the same organism prefers α(2,3) linkage over substrates with the other two linkage types [2].
+GH33 includes most bacterial and simple eukaryotic sialidases and trans-sialidases <cite> Amaya2004</cite>. Members of GH33 exhibit different preferences for the three most common sialic acid linkage types listed above, despite similar protein structure. For example, sialidases from ''Salmonella typhimurium'' LT2, ''Vibrio Cholerae'', and ''Clostridium septicum'', ''Clostridium sordellii'', ''Clostridium chauvoei'', ''Clostridium tertium'' demonstrate a higher hydrolysis activity towards α(2,3) linked substrates than α(2,6) linked substrates, while sialidases from ''Corynebacteriumm diphtheria'' and ''Micromonospora viridifaciens'' prefer to hydrolyze substrates with α(2,6) linkages <cite> Kim2011</cite>. One organism may produce sialidase isoenzymes with different substrate preferences. ''Pasteurella multocida'' produces two sialidases with different substrate preferences: NanH, an extracellular enzyme favouring α(2,3)-linked sialyllactose over α(2,6)-linked sialyllactose and NanB, a membrane bound enzyme that prefers α(2,6)-linked substrates over α(2,3)-linked substrates  cite> Mizan2000</cite>. Similarly, membrane-bound NanA of ''Salmonella pneumoniae'' displays similar hydrolysis rates for sialyllactoses with α(2,3)-, α(2,6)- and α(2,8)-linkages whereas  extracellular NanB from the same organism prefers α(2,3) linkage over substrates with the other two linkage types <cite> Kim2011</cite>.
 == Kinetics and Mechanism ==
-Content is to be added here.
+Sialidases and trans-sialidases hydrolyse or transfer sialic acids with retention of the anomeric configuration. Considerable debate had occurred over whether an ionic or covalent intermediate was formed. However, a glycosyl-enzyme intermediate was observed on T. cruzi trans-sialidase(TcTS) by mass spectrometry using a fluorinated sialic acid analogue, and a crystal structure determined <cite> Amaya2004 Watts2003</cite> Kinetic analysis of TcTS revealed a 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> Watts2008</cite> and Clostridium perfringens <cite> Newstead2008</cite> also characterised their covalent intermediates.
@@ Line 58: / Line 59: @@
 #Buschiazzo2008 pmid=18625334
 #Amaya2004 pmid=15130470
+#Mizan2000 pmid=11092845
+#Watts2003 pmid=12812490
+#Damager2008 pmid=18284211
+#Watts2006 pmid=16298994
+#Newstead2008 pmid=18218621
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH033]]