Lipases/acyltransferases homologous to CpLIP2 from Candida parapsilosis belong to the α/β hydrolase superfamily as lipase A from Moesziomyces antarcticus (Candida antarctica), and constitute a consistent phylogenetic subgroup with at least 56% identity. Lipases/acyltransferases share the phenotypic characteristic of a high acyltransfer activity even in aqueous media with very high water thermodynamic activity. Previous mutagenesis and evolution strategies have given insights into the role of key residues and protein subdomains in the reaction and substrate specificities of these enzymes. However, multiple mutations are often deleterious for the activity and the identification of all the residues that historically led to the function is complicated. A new complementary approach to elucidate structural determinant was conducted in this study, based on the resurrection of ancestral proteins to understand how the evolution led to the present properties of the biocatalysts. By doing so, the comparison with the extant proteins can lead to the identification of key residues involved in the enzymes' specialization. Using Ancestral Sequence Reconstruction, we have generated a putative ancestral lipases/acyltransferases, PaleoLAc. This enzyme shares a high level of identity with CpLIP2 but has a different catalytic behavior. PaleoLAc allowed the identification of putative key residues involved in acyltransfer ability and supports the hypothesis that this exceptional property within the lipases/acyltransferases family is linked to a cluster of residues in the vicinity of the active site. As a representative of the ancestral origin of the diversity of the catalytic behaviors observed in modern lipases/acyltransferases, PaleoLAc constitutes a powerful tool for further engineering toward targeted specialization.
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http://dx.doi.org/10.1016/j.bbapap.2017.06.004 | DOI Listing |
BMC Biol
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State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
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December 2024
School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Road, Yinchuan, 750004, Ningxia, China.
The development of phosphorylation-suppressing inhibitors targeting Signal Transducer and Activator of Transcription 3 (STAT3) represents a promising therapeutic strategy for non-small cell lung cancer (NSCLC). In this study, a generative model was developed using transfer learning and virtual screening, leveraging a comprehensive dataset of STAT3 inhibitors to explore the chemical space for novel candidates. This approach yielded a chemically diverse library of compounds, which were prioritized through molecular docking and molecular dynamics (MD) simulations.
View Article and Find Full Text PDFJ Agric Food Chem
December 2024
Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey 08901, United States.
Through a quantitative analysis of saltiness perception, favorable enzymatic hydrolysis parameters were confirmed for the preparation of saltiness-enhancing peptide mixtures from . The enzymatic hydrolysate was fractionated into four fractions (F1-F4) by gel chromatography, with F3 exhibiting the strongest saltiness-enhancing effect (22% increase). LC-MS/MS analysis of F3 identified 36 peptides, and their secondary structures and interactions with the TMC4 receptor were examined through circular dichroism spectroscopy and molecular docking.
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December 2024
Noakhali Science and Technology University, Microbiology, Sonapur, Noakhali, BANGLADESH.
Cryptococcus neoformans, the most opportunistic fungal pathogen, causes cryptococcal meningitis. Based on molecular docking and ADME/toxicity analysis, the top two lead compounds selected from a screening of 5,807 phytochemical compounds from 29 medicinal plants were CID_8299 and CID_71346280, with docking scores of -5.786 and -6.
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December 2024
Central China Normal University, State Key Laboratory of Green Pesticide, CHINA.
Butyrylcholinesterase plays an indispensable role in organisms, and its abnormal expression poses a significant threat to human health and safety, covering various aspects including liver-related diseases, diabetes, obesity, cardiovascular and cerebrovascular diseases, and neurodegenerative diseases. In addition, toxic substances such as organophosphorus and carbamate pesticides markedly inhibit BChE activity. BChE activity serves as a critical parameter for the clinical diagnosis of acute organophosphorus pesticide poisoning and the evaluation of organophosphorus and carbamate pesticide residues.
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