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SHR Neuro Cancer Cardio Lipid Metab Microb

Eisner, H; Riegler-Berket, L; Gamez, CFR; Sagmeister, T; Chalhoub, G; Darnhofer, B; Jazleena, PJ; Birner-Gruenberger, R; Pavkov-Keller, T; Haemmerle, G; Schoiswohl, G; Oberer, M.
The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1.
Int J Mol Sci. 2022; 23(21): Doi: 10.3390/ijms232113101 [OPEN ACCESS]
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Co-authors Med Uni Graz
Birner-Grünberger Ruth
Darnhofer Barbara
Riegler-Berket Lina
Schoiswohl Gabriele Maria
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Abstract:
Members of the carboxylesterase 2 (Ces2/CES2) family have been studied intensively with respect to their hydrolytic function on (pro)drugs, whereas their physiological role in lipid and energy metabolism has been realized only within the last few years. Humans have one CES2 gene which is highly expressed in liver, intestine, and kidney. Interestingly, eight homologous Ces2 (Ces2a to Ces2h) genes exist in mice and the individual roles of the corresponding proteins are incompletely understood. Mouse Ces2c (mCes2c) is suggested as potential ortholog of human CES2. Therefore, we aimed at its structural and biophysical characterization. Here, we present the first crystal structure of mCes2c to 2.12 Å resolution. The overall structure of mCes2c resembles that of the human CES1 (hCES1). The core domain adopts an α/β hydrolase-fold with S230, E347, and H459 forming a catalytic triad. Access to the active site is restricted by the cap, the flexible lid, and the regulatory domain. The conserved gate (M417) and switch (F418) residues might have a function in product release similar as suggested for hCES1. Biophysical characterization confirms that mCes2c is a monomer in solution. Thus, this study broadens our understanding of the mammalian carboxylesterase family and assists in delineating the similarities and differences of the different family members.
Find related publications in this database (using NLM MeSH Indexing)
Humans - administration & dosage
Mice - administration & dosage
Animals - administration & dosage
Carboxylic Ester Hydrolases - genetics, metabolism
Carboxylesterase - genetics, metabolism
Hydrolysis - administration & dosage
Intestines - administration & dosage
Liver - metabolism
Mammals - metabolism

Find related publications in this database (Keywords)
carboxylesterase 2c
protein structure
lipid metabolism
X-ray crystallography
alpha/beta-hydrolase fold
biochemistry
lipid hydrolysis
non-alcoholic fatty liver disease
molnupiravir
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