Carbohydrate Esterase Family 1

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.

• Author: ^^^Casper Wilkens^^^
• Responsible Curator:

---

Carbohydrate Esterase Family 1
Clan	GH-x
Mechanism	retaining/inverting
Active site residues	known/not known
CAZy DB link
https://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, the general mechanism of hydrolysis, involving the serine nucleophile, an activating histidine, and a catalytic acid, appears to be conserved. 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 [2, 3].

Catalytic Residues

The serine nucleophile 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 [2].

Three-dimensional structures

CE1's are members of the α/β-hydrolase superfamily [4], which are comprised of a central β-sheet with 8 or 9 strands connected by α-helices [5].

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 [4].

First 3-D structure

Mycobacterium tuberculosis H37Rv mycolyltransferase crystal structure in 2000 [4].

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. 2014;42(Database issue):D490-5. DOI:10.1093/nar/gkt1178 |
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. 2001;40(42):12524-32. DOI:10.1021/bi011391c |
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. 2001;9(12):1183-90. DOI:10.1016/s0969-2126(01)00684-0 |
4. 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. 2000;7(2):141-6. DOI:10.1038/72413 |
5. 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. 1992;5(3):197-211. DOI:10.1093/protein/5.3.197 |
6. 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. 1997;276(5317):1420-2. DOI:10.1126/science.276.5317.1420 |