From transglutaminases (TGs) to arylamine N-acetyltransferases (NATs): Insight into the role of a spatially conserved aromatic amino acid position in the active site of these two families of enzymes
| Autor: | Jean-Marie Dupret, Christina Michail, Rongxing Liu, Ximing Xu, Alain Chaffotte, Fernando Rodrigues-Lima, Jérémy Berthelet, Wenchao Zhang |
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| Přispěvatelé: | Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Ocean University of China (OUC), Résonance Magnétique Nucléaire des Biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
PRODY Arylamine N-Acetyltransferase Stereochemistry [SDV]Life Sciences [q-bio] Biophysics PROTEIN METABOLISM Biochemistry Amino Acids Aromatic 03 medical and health sciences chemistry.chemical_compound Residue (chemistry) 0302 clinical medicine DOMAIN Catalytic Domain Catalytic triad COFACTOR RECOGNITION BINDING Aromatic amino acids Animals Humans Amino Acid Sequence Molecular Biology Conserved Sequence chemistry.chemical_classification Transglutaminases biology IDENTIFICATION Tryptophan Active site Acetyltransferases Cell Biology EVOLUTION TRYPTOPHAN [SDV] Life Sciences [q-bio] 030104 developmental biology Enzyme chemistry 030220 oncology & carcinogenesis Biocatalysis biology.protein Cysteine |
| Zdroj: | Biochemical and Biophysical Research Communications Biochemical and Biophysical Research Communications, Elsevier, 2020, 525 (2), pp.308-312. ⟨10.1016/j.bbrc.2020.02.082⟩ Biochemical and Biophysical Research Communications, 2020, 525 (2), pp.308-312. ⟨10.1016/j.bbrc.2020.02.082⟩ |
| ISSN: | 0006-291X 1090-2104 |
| DOI: | 10.1016/j.bbrc.2020.02.082⟩ |
| Popis: | International audience; Transglutaminases (TG) and arylamine N-acetyltransferases (NAT) are important family of enzymes. Although they catalyze different reactions and have distinct structures, these two families of enzymes share a spatially conserved catalytic triad (Cys, His, Asp residues). In active TGs, a conserved Trp residue located close to the triad cysteine is crucial for catalysis through stabilization of transition states. Here, we show that in addition to sharing a similar catalytic triad with TGs, functional NAT enzymes also possess in their active site an aromatic residue (Phe, Tyr or Trp) occupying a structural position similar to the Trp residue of active TGs. More importantly, as observed in active TGs, our data indicates that in functional NAT enzymes this conserved aromatic residue is also involved in stabilization of transition states. These results thus indicate that in addition to the three triad residues, these two families of enzymes also share a spatially conserved aromatic amino acid position important for catalysis. Identification of residues involved in the stabilization of transition states is important to develop potent inhibitors. Interestingly, NAT enzymes have been shown as potential targets of clinical interest. (C) 2020 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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