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Difference between revisions of "Glycosyltransferase Family 108"

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|GH-x
 
|GH-x
 
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|'''Mechanism'''
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|inverting: GDP-Man β-1,2-mannosyltransferase (EC 2.4.99.-), donor is GDP-α-Man; 1,2-β-oligomannan phosphorylase (EC 2.4.1.340), product is α-mannose-1-phosphate
|retaining/inverting
 
 
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|'''Active site residues'''
 
|'''Active site residues'''
|known/not known
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|known
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|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
 
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
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== Substrate specificities ==
 
== Substrate specificities ==
Content is to be added here.
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The [[glycosyltransferases]] in family GT108 were originally identified by bioinformatics analysis using GH130 sequences as a query. This identified a tandem repeat of seven genes on chromosome 10 of ‘’Leishmania mexicana’’ and varying numbers of orthologs in other trypanosomatids <cite>Sernee2019</cite>. A null mutant lacking the entire array of seven genes lost the ability to synthesize 1,2-β-oligomannan (termed mannogen). These enzymes were termed mannosyltransferase/phosphorylases (MTPs) owing to ability to both synthesize mannogen from GDPMan and/or Man-1-P, as well as an ability to catalyze phosphorolysis of mannogen to form Man-1-P. Specifically, the ‘’L. Mexicana’’ enzymes MPT3, MPT4, MPT6 and MPT7 catalyzed the phosphorolysis of mannogen to give Man-1-P, as well as the reverse reaction to synthesize mannogen by mannosyltransfer from Man-1-P. The ‘’L. Mexicana’’ enzymes MPT1 and MPT2 act as GDP-Man dependent β-1,2-mannosyltransferases, elongating mannogen, and lack detectable phosphorolytic activity.
 
 
Authors may get an idea of what to put in each field from ''Curator Approved'' [[Glycosyltransferase Families]]. ''(TIP: Right click with your mouse and open this link in a new browser window...)''
 
 
 
In the meantime, please see these references for an essential introduction to the CAZy classification system: <cite>DaviesSinnott2008 Cantarel2009</cite>.
 
  
 
== Kinetics and Mechanism ==
 
== Kinetics and Mechanism ==
Content is to be added here.
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In the glycoside cleavage reaction this residue acts as a [[general acid]], protonating the glycosidic leaving group via a proton relay through the -1 subsite mannose 3-OH, allowing phosphate to displace the anomeric glycoside leaving group. In the reverse reaction involving mannosyl transfer from Man-1-P (or GDP-Man for MPT1 and 2), this residue acts as a [[general base]], deprotonating the 2-OH of the sugar nucleophile to promote glycosidic bond formation. The proposed mechanism is similar to that for family [[GH130]] β-1,2-mannoside phosphorylases <cite> Nakae2013</cite>
  
 
== Catalytic Residues ==
 
== Catalytic Residues ==
Content is to be added here.
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Asp83 is the catalytic general base in the ''Leishmania mexicana’’ MPT4. The GDP-Man transferases MTP1 and MTP2 contain a His residue (His168 in MTP1 and His161 in MTP2) in the active site; at the equivalent position the phosphorolytic MTPs such as MTP4 contain an Arg residue (Arg150).  
  
 
== Three-dimensional structures ==
 
== Three-dimensional structures ==
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== Family Firsts ==
 
== Family Firsts ==
;First stereochemistry determination: Content is to be added here.
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;First catalytic residue identification: Asp83 in ‘’Leishmania mexicana’’ MPT4 and other MPT enzymes <cite>Sernee2019</cite>. The His/Arg switch distinguishing GDP-Man dependent transferase activity, and phosphorolytic activity was also identified in this study.
;First catalytic nucleophile identification: Content is to be added here.
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;First 3-D structure: The ‘’Leishmania major’’ strain Friedlin protein LMJF_10_1260 was determined by X-ray crystallography <cite>Holmes2005</cite>.
;First general acid/base residue identification: Content is to be added here.
 
;First 3-D structure: Content is to be added here.
 
  
 
== References ==
 
== References ==
 
<biblio>
 
<biblio>
#Cantarel2009 pmid=18838391
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#Holmes2005 2B4W, Hypothetical protein from leishmania major [http://www.rcsb.org/structure/2B4W].
#DaviesSinnott2008 Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. ''The Biochemist'', vol. 30, no. 4., pp. 26-32. [http://www.biochemist.org/bio/03004/0026/030040026.pdf Download PDF version].
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 +
#Sernee2019 pmid= 31513773
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#Nakae2013 pmid=23954514
 +
 
 
</biblio>
 
</biblio>
  
 
[[Category:Glycosyltransferase Families|GT108]]
 
[[Category:Glycosyltransferase Families|GT108]]

Revision as of 15:52, 17 September 2019

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This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.

Glycosyltransferase Family GT108
Clan GH-x
inverting: GDP-Man β-1,2-mannosyltransferase (EC 2.4.99.-), donor is GDP-α-Man; 1,2-β-oligomannan phosphorylase (EC 2.4.1.340), product is α-mannose-1-phosphate
Active site residues known
CAZy DB link
http://www.cazy.org/GT108.html


Substrate specificities

The glycosyltransferases in family GT108 were originally identified by bioinformatics analysis using GH130 sequences as a query. This identified a tandem repeat of seven genes on chromosome 10 of ‘’Leishmania mexicana’’ and varying numbers of orthologs in other trypanosomatids [1]. A null mutant lacking the entire array of seven genes lost the ability to synthesize 1,2-β-oligomannan (termed mannogen). These enzymes were termed mannosyltransferase/phosphorylases (MTPs) owing to ability to both synthesize mannogen from GDPMan and/or Man-1-P, as well as an ability to catalyze phosphorolysis of mannogen to form Man-1-P. Specifically, the ‘’L. Mexicana’’ enzymes MPT3, MPT4, MPT6 and MPT7 catalyzed the phosphorolysis of mannogen to give Man-1-P, as well as the reverse reaction to synthesize mannogen by mannosyltransfer from Man-1-P. The ‘’L. Mexicana’’ enzymes MPT1 and MPT2 act as GDP-Man dependent β-1,2-mannosyltransferases, elongating mannogen, and lack detectable phosphorolytic activity.

Kinetics and Mechanism

In the glycoside cleavage reaction this residue acts as a general acid, protonating the glycosidic leaving group via a proton relay through the -1 subsite mannose 3-OH, allowing phosphate to displace the anomeric glycoside leaving group. In the reverse reaction involving mannosyl transfer from Man-1-P (or GDP-Man for MPT1 and 2), this residue acts as a general base, deprotonating the 2-OH of the sugar nucleophile to promote glycosidic bond formation. The proposed mechanism is similar to that for family GH130 β-1,2-mannoside phosphorylases [2]

Catalytic Residues

Asp83 is the catalytic general base in the Leishmania mexicana’’ MPT4. The GDP-Man transferases MTP1 and MTP2 contain a His residue (His168 in MTP1 and His161 in MTP2) in the active site; at the equivalent position the phosphorolytic MTPs such as MTP4 contain an Arg residue (Arg150).

Three-dimensional structures

Content is to be added here.

Family Firsts

First catalytic residue identification
Asp83 in ‘’Leishmania mexicana’’ MPT4 and other MPT enzymes [1]. The His/Arg switch distinguishing GDP-Man dependent transferase activity, and phosphorolytic activity was also identified in this study.
First 3-D structure
The ‘’Leishmania major’’ strain Friedlin protein LMJF_10_1260 was determined by X-ray crystallography [3].

References

  1. pmid= 31513773
    [Sernee2019]
  2. Nakae S, Ito S, Higa M, Senoura T, Wasaki J, Hijikata A, Shionyu M, Ito S, and Shirai T. (2013) Structure of novel enzyme in mannan biodegradation process 4-O-β-D-mannosyl-D-glucose phosphorylase MGP. J Mol Biol. 425, 4468-78. DOI:10.1016/j.jmb.2013.08.002 | PubMed ID:23954514 | HubMed [Nakae2013]
  3. 2B4W, Hypothetical protein from leishmania major [1].
    [Holmes2005]