ESTHER: the database dedicated to the analysis of
protein sequences within the superfamily of alpha/beta
hydrolases and cholinesterase relatives (CHEPON2024,
poster PO31)

Arnaud Chatonnet, Zhou Yu, Nicolas Roche, Pascale Marchot

► To cite this version:

Arnaud Chatonnet, Zhou Yu, Nicolas Roche, Pascale Marchot. ESTHER: the database dedicated to the analysis of protein sequences within the superfamily of alpha/beta hydrolases and cholinesterase relatives (CHEPON2024, poster PO31). CHEPON 2024 15th International Meeting on Cholinesterases 9th International Conference on Paraoxonases, Sep 2024, Brdo pri Kranju, Slovenia. . hal-04752374

HAL Id: hal-04752374

https://cnrs.hal.science/hal-04752374v1

Submitted on 24 Oct 2024

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Distributed under a Creative Commons Attribution 4.0 International License
# ESTHER: the database dedicated to the analysis of protein sequences within the superfamily of alpha/beta hydrolases and cholinesterase relatives

Arnaud CHATONNET¹, Zhou YU², Nicolas ROCHE² and Pascale MARCHOT³

¹Dynamique du Muscle et Métabolisme, INRAE, Université Montpellier, France.

²Terre Nourricière, 26, allée de Mycènes, Montpellier, France.

³Architecture et Fonction des Macromolécules Biologiques (AFMB), CNRS Aix-Marseille Université (CNRS/AMU), Campus de Luminy, Marseille, France

DMeM
Dynamique du Muscle et Métabolisme

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AFMB

ARCHITECTURE ET FONCTION
DES MACROMOLÉCULES
BIOLOGIQUES

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UNIVERSITÉ DE
MONTPELLIER

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## Abstract.

For IT security reasons, the ESTHER database, which is dedicated to ESTerases and alpha/beta Hydrolase Enzymes and Relatives headed by the cholinesterases, switched to a new operating system in April 2024. After 30 years of using the ACEDB database system, we had to start again from scratch to warrant the quality of the transition. Thanks to the robustness of the model and data structure recovered as text files, the procedure was relatively smooth, and most of the data and tools are now operational again.

ESTHER grows at fast pace: nowadays it contains ca. 70.000 Gene-proteins, grouped in 247 families [1,2]. In 2024, the number of 3D structures available in the RCSB-PDB reached 3000, corresponding to 739 distinct proteins validated as members of the superfamily. There are 143 families in which at least one 3D structure is known, and new families are regularly added to the superfamily. For the human genome, 120 genes belong to 59 families described in the database. A 3D structure is available for only 51 proteins encoded by these genes. Mutations associated with a disease are found in 35 of the human genes. The 768 published mutations in the genes of Block C proteins (Carboxylesterase, Cholesterol_esterase, Cholinesterase, Neuroligin, Thyroglobulin...) correspond to 341 residue positions in the protein sequence of Torpedo (Tetronarce californica) acetylcholinesterase used as a reference. 112 distinct mutations in acetylcholinesterase or carboxylesterase genes where described in insecticide-resistant populations of 43 arthropod species [3].

The new version of the web server with improved layout and new tools is available at http://bioweb.supagro.inrae.fr/ESTHER. Feedbacks from the users on this rejuvenated ESTHER will be most welcome

<figure><img src="image_6.png" /></figure>

Extract from the "Overall table" page of Esther where families are grouped in blocks, higher rank families and sub-families. A pop-up window shows a short outline of the specificity of the family. Family name is an hyperlink to the family web page. Various colored buttons lead to substrate, mutations, structures, disease and taxonomic coverage data respectively, as well as to links to corresponding families in Pfam, Interpro, and Prosite external databases.

Extract from the old "Tree" page of ESTHER Similarity score between families is calculated from family's HMM HMM comparison with Hhalign software from the Max Planck Society (http://toolkit.tuebingen.mpg.de). Here is the old tree.

The tree is under construction in the new web site of ESTHER. Red, green, yellow and blue families belong to blocks C, H, L and X, respectively. The number of genes contained in each family is indicated in purple next to the family name. Letters B and S are "mouse over" web hyper links that show selected branches and species distribution of genes.

## Domain structure of families

Extract from the "All figures of families" page of Esther. The alpha/beta hydrolase domain is shown in green. (domains not on scale).

Images built with MyDomains - Image Creator from PROSITE using data from InterPro, Pfam and Uniprot (input data can be found in a file figfamily.txt which shows the choosen representative of the family, the size of domains, the positions of active site residues and disulfide bond).

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## Catalytic activity

Different classes of objects are accessible: Substrate, Inhibitor, Reactivator, Type_substrate, Type_inhibitor, Type_reactivator, Structure

## Inhibitor Page

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## Type Inhibitor Page

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## References:

[1] Chatonnet et al. The ESTHER database on alpha\/beta hydrolase fold proteins - An overview of recent developments Chem Biol Interact. 2023, 383, 110671
[2] Lenfant et al. ESTHER, the database of the alpha\/beta-hydrolase fold superfamily of proteins: tools to explore diversity of functions Nucleic Acids Res. 2013, 41, D423
[3] Hotelier et al. Insecticide resistance through mutations in cholinesterases or carboxylesterases: data mining in the ESTHER database J. Pestic. Sci. 2010, 35, 315-20

## Result of a blast search

<figure><img src="image_11.png" /><figcaption>Sequences producing significant alignments:</figcaption></figure>

<table><thead><tr><th>Sequence Description</th><th>Total score</th><th>Query cover</th><th>E Value</th><th>Ident</th><th>Accession</th></tr></thead><tbody><tr><td>IF1/ Pan troglodytes (Chimpanzee) acetylcholinesterase</td><td>1252</td><td>100%</td><td>0.0</td><td>100%</td><td>pantr-ACHE</td></tr><tr><td>IF1/ Homo sapiens (Human) acetylcholinesterase</td><td>1252</td><td>100%</td><td>0.0</td><td>100%</td><td>human-ACHE</td></tr><tr><td>IF1/ Gorilla gorilla (Lowland gorilla) Uncharacterized protein</td><td>1252</td><td>100%</td><td>0.0</td><td>100%</td><td>gongo-ACHE</td></tr><tr><td>IF1/ Rhinopithecus bieti (Black snub-nosed monkey) (Pygathrix bieti); Rhinopithecus roxellana (Golden snub-nosed monkey) (Pygathrix rox...)</td><td>1246</td><td>100%</td><td>0.0</td><td>100%</td><td>rhibe-ACHE</td></tr><tr><td>IF1/ Pongo abellii (Sumatran orangutan) (Pongo pygmaeus abellii) acetylcholinesterase</td><td>1245</td><td>100%</td><td>0.0</td><td>99%</td><td>ponab-ACHE</td></tr><tr><td>IF1/ Macaca mulatta (Rhesus macaque) acetylcholinesterase gene complete cds</td><td>1245</td><td>100%</td><td>0.0</td><td>100%</td><td>macmu-ACHE</td></tr><tr><td>IF1/ Papio anubis (Olive baboon). Carboxylic ester hydrolase</td><td>1241</td><td>100%</td><td>0.0</td><td>99%</td><td>papan-a0a096nsg1</td></tr><tr><td>IF1/ Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus). Carboxylic ester hydrolase</td><td>1241</td><td>100%</td><td>0.0</td><td>99%</td><td>chlsb-a0a0d9rzh8</td></tr><tr><td>IF1/ Cercacebus atys (Sooty mangabey) (Cercacebus torquatus atys). Acetylcholinesterase</td><td>1241</td><td>100%</td><td>0.0</td><td>99%</td><td>cerat-a0a2k5p015</td></tr><tr><td>IF1/ Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey). Macaca nemestrina (Pig-tailed macaque) Putative uncharacterized...</td><td>1237</td><td>100%</td><td>0.0</td><td>99%</td><td>macfa-g8f585</td></tr><tr><td>IF1/ Aotus nancymae (Ma's night monkey) acetylcholinesterase</td><td>1203</td><td>100%</td><td>0.0</td><td>95%</td><td>aotna-a0a2k5ep18</td></tr><tr><td>IF1/ Nomascus leucogenys (Northern white-cheeked gibbon) (Hylobates leucogenys) Uncharacterized protein</td><td>1161</td><td>93%</td><td>0.0</td><td>99%</td><td>nomle-g1fmy6</td></tr><tr><td>IF1/ Mandrillus leucophaeus (Drill) (Papio leucophaeus). Carboxylic ester hydrolase</td><td>1149</td><td>93%</td><td>0.0</td><td>99%</td><td>manle-a0a2k5xi20</td></tr><tr><td>IF1/ Mustela putorius furo (European domestic ferret) (Mustela furo) Uncharacterized protein</td><td>1148</td><td>100%</td><td>0.0</td><td>93%</td><td>muspf-m3ywm4</td></tr><tr><td>IF1/ Tupaia chinensis (Chinese tree shrew) Acetylcholinesterase</td><td>1145</td><td>100%</td><td>0.0</td><td>94%</td><td>tupch-49k1d4</td></tr></tbody></table>

## Perspectives

Many pages from the old site still need to be implemented or corrected (queries, all structures; Hall of fame.... etc....)