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Difference between revisions of "Carbohydrate Esterase Family 1"

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{{UnderConstruction}}
 
{{UnderConstruction}}
 
* [[Author]]: ^^^Casper Wilkens^^^
 
* [[Author]]: ^^^Casper Wilkens^^^
* [[Responsible Curator]]:
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* [[Responsible Curator]]: ^^^Harry Brumer^^^
 
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|-
 
|-
 
|'''Clan'''     
 
|'''Clan'''     
|GH-x
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|α/β-hydrolase superfamily
 
|-
 
|-
 
|'''Mechanism'''
 
|'''Mechanism'''
|retaining/inverting
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|serine hydrolase
 
|-
 
|-
 
|'''Active site residues'''
 
|'''Active site residues'''
|known/not known
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|known
 
|-
 
|-
 
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
 
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
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== Kinetics and Mechanism ==
 
== Kinetics and Mechanism ==
CE1 enzymes target a large variety of substrates, however, the general mechanism of hydrolysis, involving the serine [[general base]], a histidine acting as general acid-base catalyst, and a [[general acid]], appears to be conserved <cite>Schubot2001 Prates2001</cite>. The [[general acid]] is structurally conserved, but both aspartic and glutamic acid are commonly observed in the position <cite>Holck2019</cite>  After substrate binding, the serine is activated by the histidine, which allows the nucleophilic attack of the substrate’s carbonyl carbon atom leading to the formation of a covalent acyl-enzyme intermediate via tetrahedral transition states sometimes known as the “tetrahedral intermediates.” Simultaneously, a proton is transferred from the serine to the histidine. The resulting tetrahydral intermediate, negatively charged carbonyl oxygen atom (“oxyanion”) is stabilized through interactions with two main chain NH groups in the “oxyanion hole”, while the positively charged histidine is stabilized by a hydrogen bond to the catalytic acid. In the next step, the formed alcohol is released from the substrate and the acid part forms an ester bond with the serine oxygen. This bond, in turn, is hydrolyzed in a two- step mechanism involving a water molecule, and the enzyme is returned to the starting point <cite>Schubot2001 Prates2001</cite>.           
+
CE1 enzymes target a large variety of substrates, however, all appear to utilize the canonical serine hydrolase mechanism, involving a catalytic triad comprising a nucleophilic serine, a histidine, and an acidic amino acid <cite>Schubot2001 Prates2001</cite>. Both aspartic and glutamic acid are commonly observed in the position <cite>Holck2019</cite>. After substrate binding, the serine is activated by the proton relay consisting of the histidine and the acid residue, which facilitates nucleophilic attack of the carbonyl carbon atom of the substrate.  This results in the formation of a covalent acyl-enzyme intermediate via a tetrahedral transition state (sometimes known as the "tetrahedral intermediate"), which is stabilized through interactions with two main-chain NH groups in the "oxyanion hole." Following release of the corresponding alcohol as the first product, the acyl-enzyme intermediate is hydrolyzed by the near-microscopic reverse of the first step, with water, activated by the proton relay, acting as the nucleophile <cite>Schubot2001 Prates2001</cite>.           
  
 
== Catalytic Residues ==
 
== Catalytic Residues ==
The serine [[general base]] is located at the center of a universally conserved pentapeptide with the consensus sequence G-X-S-X-G. This pentapeptide segment constitutes the so-called “nucleophilic elbow”, which has become the fingerprint feature commonly used to identify proteins of this enzyme family based on their primary structure alone <cite>Schubot2001</cite>. The histidine acting as general acid-base catalyst is also conserved <cite>Schubot2001 Prates2001</cite>, while the [[general acid]] commonly is observed as both a aspartic or glutamic acid <cite>Holck2019</cite>.           
+
The catalytic serine is located at the center of a universally conserved pentapeptide with the consensus sequence G-X-S-X-G. This pentapeptide segment constitutes the so-called "nucleophilic elbow", which serves as a fingerprint feature commonly used to identify proteins of this enzyme family based on their primary structure alone <cite>Schubot2001</cite>. The histidine is also conserved <cite>Schubot2001 Prates2001</cite>, while the [[general acid]] may be an aspartic acid or glutamic acid <cite>Holck2019</cite>.           
  
 
== Three-dimensional structures ==
 
== Three-dimensional structures ==
CE1's are members of the α/β-hydrolase superfamily <cite>Ronning2000</cite>, which are comprised of a central β-sheet with 8 or 9 strands connected by α-helices <cite>Ollis1992</cite>. A number of CE1 enzymes have a [[CBM48]] appended, which proved to be essential for these feruloyl esterases acticity on polymeric xylan <cite>Holck2019</cite>.
+
CE1 is a member of the α/β-hydrolase superfamily <cite>Ronning2000</cite>, which are comprised of a central β-sheet with 8 or 9 strands connected by α-helices <cite>Ollis1992</cite>. A number of CE1 enzymes have a [[CBM48]] appended that proved to be essential for feruloyl esterase activity on polymeric xylan <cite>Holck2019</cite>.
  
 
== Family Firsts ==
 
== Family Firsts ==
 
;First characterized: Content is to be added here.
 
;First characterized: Content is to be added here.
;First mechanistic insight: The crystal structure of           ''Mycobacterium'' ''tuberculosis'' H37Rv mycolyltransferase in complex with the covalently bound inhibitor, diethyl phosphate gave the first insight into the mechanism, which involved the highly conserved catalytic Ser-Glu-His triad             <cite>Ronning2000</cite>.
+
;First mechanistic insight: The crystal structure of ''Mycobacterium'' ''tuberculosis'' H37Rv mycolyltransferase in complex with the covalently bound inhibitor, diethyl phosphate gave the first insight into the mechanism, which involved the highly conserved catalytic Ser-Glu-His triad <cite>Ronning2000</cite>.
 
;First 3-D structure: ''Mycobacterium'' ''tuberculosis'' H37Rv mycolyltransferase crystal structure in 2000  <cite>Ronning2000</cite>.
 
;First 3-D structure: ''Mycobacterium'' ''tuberculosis'' H37Rv mycolyltransferase crystal structure in 2000  <cite>Ronning2000</cite>.
  
 
== References ==
 
== References ==
 
<biblio>
 
<biblio>
 
 
#Lombard2014 pmid=24270786
 
#Lombard2014 pmid=24270786
 
 
#Ronning2000 pmid=10655617
 
#Ronning2000 pmid=10655617
 
#Belisle1997 pmid=9162010
 
#Belisle1997 pmid=9162010
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#Prates2001 pmid=11738044
 
#Prates2001 pmid=11738044
 
#Schubot2001 pmid=11601976
 
#Schubot2001 pmid=11601976
 
 
#Holck2019 pmid=31558605
 
#Holck2019 pmid=31558605
 
 
</biblio>
 
</biblio>
 
[[Category:Carbohydrate Esterase Families|CE001]]
 
[[Category:Carbohydrate Esterase Families|CE001]]

Latest revision as of 13:26, 23 March 2020

Under construction icon-blue-48px.png
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.

Carbohydrate Esterase Family 1
Clan α/β-hydrolase superfamily
Mechanism serine hydrolase
Active site residues known
CAZy DB link
http://www.cazy.org/CE1.html


Substrate specificities

Carbohydrate esterase family 1 (CE1) is one of the biggest and most diverse CE families including acetylxylan esterases (EC 3.1.1.72), feruloyl esterases (EC 3.1.1.73), cinnamoyl esterases (EC 3.1.1.-), carboxylesterases (EC 3.1.1.1), S-formylglutathione hydrolases (EC 3.1.2.12), diacylglycerol O-acyltransferases (EC 2.3.1.20), and thehalose 6-O-mycolyltransferases (EC 2.3.1.122) and others [1].

Kinetics and Mechanism

CE1 enzymes target a large variety of substrates, however, all appear to utilize the canonical serine hydrolase mechanism, involving a catalytic triad comprising a nucleophilic serine, a histidine, and an acidic amino acid [2, 3]. Both aspartic and glutamic acid are commonly observed in the position [4]. After substrate binding, the serine is activated by the proton relay consisting of the histidine and the acid residue, which facilitates nucleophilic attack of the carbonyl carbon atom of the substrate. This results in the formation of a covalent acyl-enzyme intermediate via a tetrahedral transition state (sometimes known as the "tetrahedral intermediate"), which is stabilized through interactions with two main-chain NH groups in the "oxyanion hole." Following release of the corresponding alcohol as the first product, the acyl-enzyme intermediate is hydrolyzed by the near-microscopic reverse of the first step, with water, activated by the proton relay, acting as the nucleophile [2, 3].

Catalytic Residues

The catalytic serine is located at the center of a universally conserved pentapeptide with the consensus sequence G-X-S-X-G. This pentapeptide segment constitutes the so-called "nucleophilic elbow", which serves as a fingerprint feature commonly used to identify proteins of this enzyme family based on their primary structure alone [2]. The histidine is also conserved [2, 3], while the general acid may be an aspartic acid or glutamic acid [4].

Three-dimensional structures

CE1 is a member of the α/β-hydrolase superfamily [5], which are comprised of a central β-sheet with 8 or 9 strands connected by α-helices [6]. A number of CE1 enzymes have a CBM48 appended that proved to be essential for feruloyl esterase activity on polymeric xylan [4].

Family Firsts

First characterized
Content is to be added here.
First mechanistic insight
The crystal structure of Mycobacterium tuberculosis H37Rv mycolyltransferase in complex with the covalently bound inhibitor, diethyl phosphate gave the first insight into the mechanism, which involved the highly conserved catalytic Ser-Glu-His triad [5].
First 3-D structure
Mycobacterium tuberculosis H37Rv mycolyltransferase crystal structure in 2000 [5].

References

  1. Lombard V, Golaconda Ramulu H, Drula E, Coutinho PM, and Henrissat B. (2014) The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 42, D490-5. DOI:10.1093/nar/gkt1178 | PubMed ID:24270786 | HubMed [Lombard2014]
  2. Schubot FD, Kataeva IA, Blum DL, Shah AK, Ljungdahl LG, Rose JP, and Wang BC. (2001) Structural basis for the substrate specificity of the feruloyl esterase domain of the cellulosomal xylanase Z from Clostridium thermocellum. Biochemistry. 40, 12524-32. DOI:10.1021/bi011391c | PubMed ID:11601976 | HubMed [Schubot2001]
  3. Prates JA, Tarbouriech N, Charnock SJ, Fontes CM, Ferreira LM, and Davies GJ. (2001) The structure of the feruloyl esterase module of xylanase 10B from Clostridium thermocellum provides insights into substrate recognition. Structure. 9, 1183-90. DOI:10.1016/s0969-2126(01)00684-0 | PubMed ID:11738044 | HubMed [Prates2001]
  4. Holck J, Fredslund F, Møller MS, Brask J, Krogh KBRM, Lange L, Welner DH, Svensson B, Meyer AS, and Wilkens C. (2019) A carbohydrate-binding family 48 module enables feruloyl esterase action on polymeric arabinoxylan. J Biol Chem. 294, 17339-17353. DOI:10.1074/jbc.RA119.009523 | PubMed ID:31558605 | HubMed [Holck2019]
  5. Ronning DR, Klabunde T, Besra GS, Vissa VD, Belisle JT, and Sacchettini JC. (2000) Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines. Nat Struct Biol. 7, 141-6. DOI:10.1038/72413 | PubMed ID:10655617 | HubMed [Ronning2000]
  6. Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, and Schrag J. (1992) The alpha/beta hydrolase fold. Protein Eng. 5, 197-211. DOI:10.1093/protein/5.3.197 | PubMed ID:1409539 | HubMed [Ollis1992]
  7. Belisle JT, Vissa VD, Sievert T, Takayama K, Brennan PJ, and Besra GS. (1997) Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science. 276, 1420-2. DOI:10.1126/science.276.5317.1420 | PubMed ID:9162010 | HubMed [Belisle1997]
All Medline abstracts: PubMed | HubMed