Golgi alpha-mannosidase II (GMII), a zinc-dependent glycosyl hydrolase, is a promising target for drug development in anti-tumor therapies. Using X-ray crystallography, we have determined the structure of Drosophila melanogaster GMII (dGMII) complexed with three different inhibitors exhibiting IC50's ranging from 80 to 1000 microM. These structures, along with those of seven other available dGMII/inhibitor complexes, were then used as a basis for the evaluation of seven docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS, LigandFit, and FITTED). We found that small inhibitors could be accurately docked by most of the software, while docking of larger compounds (i.e., those with extended aromatic cycles or long aliphatic chains) was more problematic. Overall, Glide provided the best docking results, with the most accurately predicted binding around the active site zinc atom. Further evaluation of Glide's performance revealed its ability to extract active compounds from a benchmark library of decoys.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/prot.21479 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification and validation of CDK1 as a promising therapeutic target for Eriocitrin in colorectal cancer: a combined bioinformatics and experimental approach.
BMC Cancer
January 2025
Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, P. R. China.
Background: Colorectal cancer (CRC) is a prevalent malignancy worldwide, associated with significant morbidity and mortality. Cyclin-dependent kinase 1 (CDK1) plays a crucial role in cell cycle regulation and has been implicated in various cancers. This study aimed to evaluate the prognostic value of CDK1 in CRC and to identify traditional Chinese medicines (TCM) that can target CDK1 as potential treatments for CRC.
View Article and Find Full Text PDFSubstituted piperazine conjugated to quinoline-thiosemicarbazide as potent α-glucosidase inhibitors to target hyperglycemia.
Sci Rep
January 2025
Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, P. O. Box 33, Nizwa, Oman.
Diabetes mellitus, particularly type 2 diabetes, is a growing global health challenge characterized by chronic hyperglycemia due to insulin resistance. One therapeutic approach to managing this condition is the inhibition of α-glucosidase, an enzyme involved in carbohydrate digestion, to reduce postprandial blood glucose levels. In this study, a series of thiosemicarbazide-linked quinoline-piperazine derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity, to identify new agents for type 2 diabetes management.
View Article and Find Full Text PDFIntegrating machine learning and structure-based approaches for repurposing potent tyrosine protein kinase Src inhibitors to treat inflammatory disorders.
Sci Rep
January 2025
State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
Tyrosine-protein kinase Src plays a key role in cell proliferation and growth under favorable conditions, but its overexpression and genetic mutations can lead to the progression of various inflammatory diseases. Due to the specificity and selectivity problems of previously discovered inhibitors like dasatinib and bosutinib, we employed an integrated machine learning and structure-based drug repurposing strategy to find novel, targeted, and non-toxic Src kinase inhibitors. Different machine learning models including random forest (RF), k-nearest neighbors (K-NN), decision tree, and support vector machine (SVM), were trained using already available bioactivity data of Src kinase targeting compounds.
View Article and Find Full Text PDF[Metabolomics combined with bioinformatics reveals mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease].
Zhongguo Zhong Yao Za Zhi
December 2024
Changzhou Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Changzhou 213000, China.
This article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD) based on metabolomics and bioinformatics. The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study. The patients were treated with Sanhuang Hushen Fangshuai Decoction, and the therapeutic effect was evaluated.
View Article and Find Full Text PDFCorydalis decumbens and tetrahydropalmatrubin inhibit macrophages inflammation to relieve rheumatoid arthritis by targeting Fosl2.
J Ethnopharmacol
January 2025
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. Electronic address:
Ethnopharmacological Relevance: Corydalis decumbens (Thunb.) (CD) is a traditional Chinese medicine and as a single herb or formula has been used to treat RA for decades. Rheumatoid arthritis (RA) is a persistent, systemic autoimmune inflammatory disease.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!