Carbohydrate Esterase Family 4 - Revision history

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

2021-12-18T21:19:08Z

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

Michael Suits at 16:33, 4 February 2019

2019-02-04T16:33:27Z

Alex Anderson at 20:57, 16 January 2019

2019-01-16T20:57:09Z

Harry Brumer: fixed Family Firsts list formatting

2018-10-18T00:33:07Z

fixed Family Firsts list formatting

Alex Anderson at 18:04, 31 August 2018

2018-08-31T18:04:01Z

Alex Anderson at 21:53, 2 August 2018

2018-08-02T21:53:17Z

Alex Anderson at 17:26, 20 July 2018

2018-07-20T17:26:18Z

Alex Anderson at 17:34, 18 July 2018

2018-07-18T17:34:41Z

Harry Brumer: Created page with " {{UnderConstruct..."

2018-05-30T11:46:44Z

Created page with " {{UnderConstruct..."

New page

{{UnderConstruction}}
* [[Author]]: ^^^Alex Anderson^^^
* [[Responsible Curator]]: ^^^Michael Suits^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Carbohydrate Esterase Family 4'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining/inverting
|-
|'''Active site residues'''
|known/not known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CE4.html
|}
</div>


== Substrate specificities ==
Content is to be added here.

Authors may get an idea of what to put in each field from ''Curator Approved'' [[Glycoside Hydrolase 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 ==
Content is to be added here.

== Catalytic Residues ==
Content is to be added here.

== Three-dimensional structures ==
Content is to be added here.

== Family Firsts ==
;First stereochemistry determination: Content is to be added here.
;First catalytic nucleophile identification: Content is to be added here.
;First general acid/base residue identification: Content is to be added here.
;First 3-D structure: Content is to be added here.

== References ==
<biblio>
#Cantarel2009 pmid=18838391
#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].
</biblio>

[[Category:Carbohydrate Esterase Families|CE004]]

@@ Line 40: / Line 40: @@
 == Family Firsts ==
-;First characterized
+;First characterized: TLC and HPLC experiments demonstrated that rhizobial NodB was a chitooligosaccharide deacetylase, and that it did not deacetylate GlcNAc monomers, only chitooligomers, and only at their nonreducing end <cite>John1993</cite>.
-TLC and HPLC experiments demonstrated that rhizobial NodB was a chitooligosaccharide deacetylase, and that it did not deacetylate GlcNAc monomers, only chitooligomers, and only at their nonreducing end <cite>John1993</cite>.
+;First mechanistic insight: The highly conserved His-His-Asp triad and His-Asp acid/base pair were first demonstrated to be catalytic in the structure of the SpPdgA peptidoglycan deacetylase from ''S. pneumoniae'' <cite>Blair2005</cite>.
-;First mechanistic insight
+;First 3-D structure: The first CE4 structure, the peptidoglycan N-acetylmuramic acid deacetylase from ''B. subtilis'', demonstrates the canonical NodB domain adopting the (β/α)<sub>7</sub> fold, along with the His-His-Asp triad and the catalytic His/Asp acid/base pair <cite>Blair2004</cite>.
 == References ==

@@ Line 28: / Line 28: @@
 == Substrate specificities ==
-CE family 4 esterases catalyze the de-acylation of polysaccharides. Known activities of  CE family 4 members include acetylxylan esterases, chitin deacetylases, chitooligosaccharide deacetylases, and peptidoglycan deacetylases. Peptidoglycan, the essential bacterial cell wall polymer, consists of alternating β-(1,4) linked N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-muramic acid (MurNAc) <cite>Hayhurst2008</cite>. All but one of the characterized PG deacetylases belonging to CE family 4 deacetylate GlcNAc.  The one characterized exception, YfjS from ''Bacillus subtilis'', deacetylates peptidoglycan MurNAc <cite>Fukushima2005</cite>.
+CE family 4 esterases catalyze the de-acylation of polysaccharides. Known activities of  CE family 4 members include acetylxylan esterases, chitin deacetylases, chitooligosaccharide deacetylases, and peptidoglycan deacetylases. Peptidoglycan, the essential bacterial cell wall polymer, consists of alternating β-(1,4) linked N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-muramic acid (MurNAc) <cite>Hayhurst2008</cite>. All but one of the characterized PG deacetylases belonging to CE family 4 deacetylate GlcNAc.  The one characterized exception, PdaA from ''Bacillus subtilis'', deacetylates peptidoglycan MurNAc <cite>Fukushima2005</cite>.
 == Kinetics and Mechanism ==

@@ Line 28: / Line 28: @@
 == Substrate specificities ==
-CE family 4 esterases catalyze the de-acylation of polysaccharides. As of June 2018, there are 60 characterized CE4 enzymes, 18 of which are acetylxylan esterases, 15 are chitin deacetylases, 14 are chitooligosaccharide deacetylases, and 13 are peptidoglycan deacetylases. Peptidoglycan, the essential bacterial cell wall polymer, consists of alternating β-(1,4) linked N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-muramic acid (MurNAc) <cite>Hayhurst2008</cite>. All but one of the characterized PG deacetylases belonging to CE family 4 deacetylate GlcNAc.  The one characterized exception, YfjS from ''Bacillus subtilis'', deacetylates peptidoglycan MurNAc <cite>Fukushima2005</cite>.
+CE family 4 esterases catalyze the de-acylation of polysaccharides. Known activities of  CE family 4 members include acetylxylan esterases, chitin deacetylases, chitooligosaccharide deacetylases, and peptidoglycan deacetylases. Peptidoglycan, the essential bacterial cell wall polymer, consists of alternating β-(1,4) linked N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-muramic acid (MurNAc) <cite>Hayhurst2008</cite>. All but one of the characterized PG deacetylases belonging to CE family 4 deacetylate GlcNAc.  The one characterized exception, YfjS from ''Bacillus subtilis'', deacetylates peptidoglycan MurNAc <cite>Fukushima2005</cite>.
 == Kinetics and Mechanism ==

@@ Line 37: / Line 37: @@
 == Three-dimensional structures ==
-All CE4 members contain a NodB domain that houses the catalytic core. This NodB domain contains the triad responsible for coordinating the essential metal cofactor along with the catalytic acid/base pair, all of which are conserved and located in five separate motifs shared across CE4 enzymes. This NodB domain adopts a (β/α)<sub>8</sub>  fold in all known structures. A notable exception for the family is PgdA from ''Streptococcus pneumoniae'' <cite>Blair2005</cite>. PgdA, a peptidoglycan GlcNAc deacetylase, contains the canonical NodB catalytic domain at its C-terminal, but the N and C termini are at opposite ends of the barrel as compared to other known CE4 structures <cite>Blair2005</cite>. PgdA is also atypical of the family in that it possesses two accessory domains that are not found in other CE4 members, nor shown any significant predicted to homology to non-CE4 members <cite>Blair2005</cite>. Other CE family 4 enzymes show considerable structural diversity outside their catalytic NodB domain, with some representative members also containing accessory CBM <cite>Andres2014</cite>, β sandwich <cite>Arnaouteli2015</cite>, α-helical <cite>Deng2009</cite>, and α/β <cite>Blair2005</cite> domains, although they are less common. In those CE4 members that do possess accessory domains, they are typically appended to the C-terminal <cite>Nishiyama2013</cite>, although presence at the N-terminal <cite>Deng2009</cite>, or flanking the NodB domain has been observed <cite>Blair2005</cite>. The length of CE4 enzymes are thus variable, but commonly near 300 residues in a prototypical, unappended CE4 member, but can range to as large as 700 residues in those appended with accessory domain(s).
+All CE4 members contain a NodB domain that houses the catalytic core. This NodB domain contains the triad responsible for coordinating the essential metal cofactor along with the catalytic acid/base pair, all of which are conserved and located in five separate motifs shared across CE4 enzymes. This NodB domain adopts a (β/α)<sub>7</sub>  fold in all known structures. A notable exception for the family is PgdA from ''Streptococcus pneumoniae'' <cite>Blair2005</cite>. PgdA, a peptidoglycan GlcNAc deacetylase, contains the canonical NodB catalytic domain at its C-terminal, but the N and C termini are at opposite ends of the barrel as compared to other known CE4 structures <cite>Blair2005</cite>. PgdA is also atypical of the family in that it possesses two accessory domains that are not found in other CE4 members, nor shown any significant predicted to homology to non-CE4 members <cite>Blair2005</cite>. Other CE family 4 enzymes show considerable structural diversity outside their catalytic NodB domain, with some representative members also containing accessory CBM <cite>Andres2014</cite>, β sandwich <cite>Arnaouteli2015</cite>, α-helical <cite>Deng2009</cite>, and α/β <cite>Blair2005</cite> domains, although they are less common. In those CE4 members that do possess accessory domains, they are typically appended to the C-terminal <cite>Nishiyama2013</cite>, although presence at the N-terminal <cite>Deng2009</cite>, or flanking the NodB domain has been observed <cite>Blair2005</cite>. The length of CE4 enzymes are thus variable, but commonly near 300 residues in a prototypical, unappended CE4 member, but can range to as large as 700 residues in those appended with accessory domain(s).
 == Family Firsts ==
@@ Line 45: / Line 45: @@
 The highly conserved His-His-Asp triad and His-Asp acid/base pair were first demonstrated to be catalytic in the structure of the SpPdgA peptidoglycan deacetylase from ''S. pneumoniae'' <cite>Blair2005</cite>.
 ;First 3-D structure
-The first CE4 structure, the peptidoglycan N-acetylmuramic acid deacetylase from ''B. subtilis'', demonstrates the canonical NodB domain adopting the (β/α)<sub>8</sub> fold, along with the His-His-Asp triad and the catalytic His/Asp acid/base pair <cite>Blair2004</cite>.
+The first CE4 structure, the peptidoglycan N-acetylmuramic acid deacetylase from ''B. subtilis'', demonstrates the canonical NodB domain adopting the (β/α)<sub>7</sub> fold, along with the His-His-Asp triad and the catalytic His/Asp acid/base pair <cite>Blair2004</cite>.
 == References ==

@@ Line 1: / Line 1: @@
 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Alex Anderson^^^
+* [[Author]]: [[User:Alex Anderson|Alex Anderson]]
-* [[Responsible Curator]]:  ^^^Michael Suits^^^
+* [[Responsible Curator]]:  [[User:Michael Suits|Michael Suits]]
 ----

@@ Line 11: / Line 11: @@
 |{{Hl2}} colspan="2" align="center" |'''Carbohydrate Esterase Family 4'''
 |-
-|'''Clan'''
+|'''Acid/alcohol sugar substrate'''
-|GH-x
+|Alcohol
 |-
-|'''Mechanism'''
+|'''Metal-dependent'''
-|retaining/inverting
+|Yes (with exception)
 |-
 |'''Active site residues'''
-|known
+|Known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''

@@ Line 18: / Line 18: @@
 |-
 |'''Active site residues'''
-|known/not known
+|known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
@@ Line 26: / Line 26: @@
 </div>
 <!-- This is the end of the table -->
 == Substrate specificities ==
-Content is to be added here.
+CE family 4 esterases catalyze the de-acylation of polysaccharides. As of June 2018, there are 60 characterized CE4 enzymes, 18 of which are acetylxylan esterases, 15 are chitin deacetylases, 14 are chitooligosaccharide deacetylases, and 13 are peptidoglycan deacetylases. Peptidoglycan, the essential bacterial cell wall polymer, consists of alternating β-(1,4) linked N-acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-muramic acid (MurNAc) <cite>Hayhurst2008</cite>. All but one of the characterized PG deacetylases belonging to CE family 4 deacetylate GlcNAc.  The one characterized exception, YfjS from ''Bacillus subtilis'', deacetylates peptidoglycan MurNAc <cite>Fukushima2005</cite>.
 == Kinetics and Mechanism ==
-Content is to be added here.
+CE4 enzymes cleave acetyl groups by binding a catalytic water molecule on their metal cofactor <cite>Blair2005</cite> (usually Zn<sup>2+</sup>, but Co<sup>2+</sup> is observed in some structures <cite>Taylor2006</cite>). The catalytic base residue is responsible for proton abstraction from the catalytic water, and generates a nucleophilic attack on the carbonyl carbon of the acetyl substrate by that water molecule <cite>Blair2005</cite>. The resulting intermediate is a tetrahedral oxyanion, stabilized by the metal cofactor <cite>Blair2005</cite>. The catalytic acid residue then protonates the nitrogen atom of the intermediate, generating the free amine, along with the acetate product bound to the metal cofactor <cite>Blair2005</cite>.
 == Catalytic Residues ==
-Content is to be added here.
+Characterized CE4 members have been shown to possess a prototypical NodB conserved domain, containing an Asp-His-His triad responsible for coordinating a Zn<sup>2+</sup> ion, an Asp residue as the catalytic base, and a His residue as the catalytic acid <cite>Blair2005</cite>. These catalytic residues are invariant in all characterized CE4 family members, with the exception of two homologous acetylxylan esterases, the enzymes SlCE4 from ''Streptomyces lividans ''and CtCE4 from ''Clostridium thermocellum ''<cite>Taylor2006</cite>. Both SlCE4 and CtCE4 showed preference for Co<sup>2+</sup> in place of Zn<sup>2+</sup>'', ''and in CtCE4, four water molecules assisted two Asp-His residues in coordination of the Co<sup>2+</sup> in place of the His-His-Asp triad typical for the family <cite>Taylor2006</cite>.
 == Three-dimensional structures ==
-Content is to be added here.
+All CE4 members contain a NodB domain that houses the catalytic core. This NodB domain contains the triad responsible for coordinating the essential metal cofactor along with the catalytic acid/base pair, all of which are conserved and located in five separate motifs shared across CE4 enzymes. This NodB domain adopts a (β/α)<sub>8</sub>  fold in all known structures. A notable exception for the family is PgdA from ''Streptococcus pneumoniae'' <cite>Blair2005</cite>. PgdA, a peptidoglycan GlcNAc deacetylase, contains the canonical NodB catalytic domain at its C-terminal, but the N and C termini are at opposite ends of the barrel as compared to other known CE4 structures <cite>Blair2005</cite>. PgdA is also atypical of the family in that it possesses two accessory domains that are not found in other CE4 members, nor shown any significant predicted to homology to non-CE4 members <cite>Blair2005</cite>. Other CE family 4 enzymes show considerable structural diversity outside their catalytic NodB domain, with some representative members also containing accessory CBM <cite>Andres2014</cite>, β sandwich <cite>Arnaouteli2015</cite>, α-helical <cite>Deng2009</cite>, and α/β <cite>Blair2005</cite> domains, although they are less common. In those CE4 members that do possess accessory domains, they are typically appended to the C-terminal <cite>Nishiyama2013</cite>, although presence at the N-terminal <cite>Deng2009</cite>, or flanking the NodB domain has been observed <cite>Blair2005</cite>. The length of CE4 enzymes are thus variable, but commonly near 300 residues in a prototypical, unappended CE4 member, but can range to as large as 700 residues in those appended with accessory domain(s).
 == Family Firsts ==
-;First stereochemistry determination: Content is to be added here.
+;First characterized
-;First catalytic nucleophile identification: Content is to be added here.
+TLC and HPLC experiments demonstrated that rhizobial NodB was a chitooligosaccharide deacetylase, and that it did not deacetylate GlcNAc monomers, only chitooligomers, and only at their nonreducing end <cite>John1993</cite>.
-;First general acid/base residue identification: Content is to be added here.
+;First mechanistic insight
-;First 3-D structure: Content is to be added here.
+The highly conserved His-His-Asp triad and His-Asp acid/base pair were first demonstrated to be catalytic in the structure of the SpPdgA peptidoglycan deacetylase from ''S. pneumoniae'' <cite>Blair2005</cite>.
 == References ==
 <biblio>
-#Cantarel2009 pmid=18838391
+#Hayhurst2008 pmid=18784364
-#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].
+#Fukushima2005 pmid=15687192
 </biblio>
 [[Category:Carbohydrate Esterase Families|CE004]]