دورية أكاديمية
Enzyme-substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis.
| العنوان: | Enzyme-substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis. |
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| المؤلفون: | Kumar S; Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. parag@che.iitkgp.ac.in., Rao NNS; Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. parag@che.iitkgp.ac.in., Reddy KSSVP; Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. parag@che.iitkgp.ac.in., Padole MC; Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. parag@che.iitkgp.ac.in., Deshpande PA; Quantum and Molecular Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. parag@che.iitkgp.ac.in. |
| المصدر: | Physical chemistry chemical physics : PCCP [Phys Chem Chem Phys] 2023 Jan 27; Vol. 25 (4), pp. 3472-3484. Date of Electronic Publication: 2023 Jan 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 100888160 Publication Model: Electronic Cited Medium: Internet ISSN: 1463-9084 (Electronic) Linking ISSN: 14639076 NLM ISO Abbreviation: Phys Chem Chem Phys Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge [England] : Royal Society of Chemistry, c1999- |
| مواضيع طبية MeSH: | Orotic Acid*/metabolism , Orotate Phosphoribosyltransferase*/chemistry , Orotate Phosphoribosyltransferase*/metabolism, Ligands ; Binding Sites |
| مستخلص: | Orotate phosphoribosyltransferase (OPRT) catalyses the reversible phosphoribosyl transfer from α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) to orotic acid (OA) to yield orotidine 5'-monophosphate (OMP) during the de novo synthesis of nucleotides. Numerous studies have reported the inhibition of this reaction as a strategy to check diseases like tuberculosis, malaria and cancer. Insight into the inhibition of this reaction is, therefore, of urgent interest. In this study, we implemented a QM/MM framework on OPRT derived from Saccharomyces cerevisiae to obtain insights into the competitive binding of OA and OA-mimetic inhibitors by quantifying their interactions with OPRT. 4-Hydroxy-6-methylpyridin-2(1 H ) one showed the best inhibiting activity among the structurally similar OA-mimetic inhibitors, as quantified from the binding energetics. Our analysis of protein-ligand interactions unveiled the association of this inhibitory ligand with a strong network of hydrogen bonds, a large contribution of hydrophobic contacts, and bridging water molecules in the binding site. The ortho -substituted CH |
| المشرفين على المادة: | 61H4T033E5 (Orotic Acid) 0 (Ligands) EC 2.4.2.10 (Orotate Phosphoribosyltransferase) |
| تواريخ الأحداث: | Date Created: 20230113 Date Completed: 20230203 Latest Revision: 20230203 |
| رمز التحديث: | 20230203 |
| DOI: | 10.1039/d2cp05406j |
| PMID: | 36637052 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1463-9084 |
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| DOI: | 10.1039/d2cp05406j |