{PDOC00112}
{PS00122; CARBOXYLESTERASE_B_1}
{PS00941; CARBOXYLESTERASE_B_2}
{BEGIN}
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* Carboxylesterases type-B signatures *
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Higher eukaryotes have many distinct esterases. Among the different types are
those which act on carboxylic esters (EC 3.1.1.-). Carboxyl-esterases have
been classified into three categories (A, B and C) on the basis of
differential patterns of inhibition by organophosphates. The sequence of a
number of type-B carboxylesterases indicates [1,2,3] that the majority are
evolutionary related. This family currently consists of the following
proteins:
- Acetylcholinesterase (EC 3.1.1.7) (AChE) from vertebrates and from
Drosophila.
- Mammalian cholinesterase II (butyryl cholinesterase) (EC 3.1.1.8).
Acetylcholinesterase and cholinesterase II are closely related enzymes that
hydrolyze choline esters [4].
- Mammalian liver microsomal carboxylesterases (EC 3.1.1.1).
- Drosophila esterase 6, produced in the anterior ejaculatory duct of the
male insect reproductive system where it plays an important role in its
reproductive biology.
- Drosophila esterase P.
- Culex pipiens (mosquito) esterases B1 and B2.
- Myzus persicae (peach-potato aphid) esterases E4 and FE4.
- Mammalian bile-salt-activated lipase (BAL) [5], a multifunctional lipase
which catalyzes fat and vitamin absorption. It is activated by bile salts
in infant intestine where it helps to digest milk fats.
- Insect juvenile hormone esterase (JH esterase) (EC 3.1.1.59).
- Lipases (EC 3.1.1.3) from the fungi Geotrichum candidum and Candida rugosa.
- Caenorhabditis gut esterase (gene ges-1).
- Duck acyl-[acyl-carrier protein] hydrolase, medium chain (EC 3.1.2.14), an
enzyme that may be associated with peroxisome proliferation and may play a
role in the production of 3-hydroxy fatty acid diester pheromones.
- Membrane enclosed crystal proteins from slime mold. These proteins are,
most probably esterases; the vesicles where they are found have therefore
been termed esterosomes.
So far two bacterial proteins have been found to belong to this family:
- Phenmedipham hydrolase (phenylcarbamate hydrolase), an Arthrobacter oxidans
plasmid-encoded enzyme (gene pcd) that degrades the phenylcarbamate
herbicides phenmedipham and desmedipham by hydrolyzing their central
carbamate linkages.
- Para-nitrobenzyl esterase from Bacillus subtilis (gene pnbA).
The following proteins, while having lost their catalytic activity, contain a
domain evolutionary related to that of carboxylesterases type-B:
- Thyroglobulin (TG), a glycoprotein specific to the thyroid gland, which is
the precursor of the iodinated thyroid hormones thyroxine (T4) and triiodo
thyronine (T3).
- Drosophila protein neurotactin (gene nrt) which may mediate or modulate
cell adhesion between embryonic cells during development.
- Drosophila protein glutactin (gene glt), whose function is not known.
As is the case for lipases and serine proteases, the catalytic apparatus of
esterases involves three residues (catalytic triad): a serine, a glutamate or
aspartate and a histidine. The sequence around the active site serine is well
conserved and can be used as a signature pattern. As a second signature
pattern, we selected a conserved region located in the N-terminal section and
which contains a cysteine involved in a disulfide bond.
-Consensus pattern: F-[GR]-G-x(4)-[LIVM]-x-[LIV]-x-G-x-S-[STAG]-G
[S is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL members
of this family with a catalytic activity.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Consensus pattern: [EDA]-[DG]-C-L-[YTF]-[LIVT]-[DNS]-[LIV]-[LIVFYW]-x-[PQR]
[C is involved in a disulfide bond]
-Sequences known to belong to this class detected by the pattern: ALL, except
for mosquito and peach-potato aphid esterases and juvenile hormone esterases.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Note: Human esterase-D, also a type-B carboxylesterase, does not seem to be
evolutionary related.
-Expert(s) to contact by email:
Sussman J.; csjoel@weizmann.weizmann.ac.il
-Last update: April 2006 / Pattern revised.
[ 1] Myers M., Richmond R.C., Oakeshott J.G.
"On the origins of esterases."
Mol. Biol. Evol. 5:113-119(1988).
PubMed=3163407
[ 2] Krejci E., Duval N., Chatonnet A., Vincens P., Massoulie J.
"Cholinesterase-like domains in enzymes and structural proteins:
functional and evolutionary relationships and identification of a
catalytically essential aspartic acid."
Proc. Natl. Acad. Sci. U.S.A. 88:6647-6651(1991).
PubMed=1862088
[ 3] Cygler M., Schrag J.D., Sussman J.L., Harel M., Silman I.,
Gentry M.K., Doctor B.P.
"Relationship between sequence conservation and three-dimensional
structure in a large family of esterases, lipases, and related
proteins."
Protein Sci. 2:366-382(1993).
PubMed=8453375
[ 4] Lockridge O.
"Structure of human serum cholinesterase."
BioEssays 9:125-128(1988).
PubMed=3067729
[ 5] Wang C.-S., Hartsuck J.A.
"Bile salt-activated lipase. A multiple function lipolytic enzyme."
Biochim. Biophys. Acta 1166:1-19(1993).
PubMed=8431483
{END}