کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1977867 | 1061515 | 2009 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional identity of the active sites of crustacean and viral thymidylate synthases
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Thymidylate synthase (TS) catalyzes the synthesis of deoxythymidine monophosphate (dTMP), which is an essential precursor for DNA synthesis. The rationale underlying drug design is to identify compounds that differentially inhibit a viral or parasite enzyme vs. the host homologue. We studied the TS of the white spot syndrome virus (WSSV TS) and the corresponding TS from the host, the marine invertebrate shrimp Litopenaeus vannamei. TS is the only de novo source of dTMP and is essential for host and viral DNA replication. To establish proof of principle, we cloned a full-length TS cDNA from the white shrimp L. vannamei (shrimp TS) that corresponds to a deduced sequence of 289 amino acids and over-expressed it to study inhibition of both shrimp and viral TSs. Steady-state kinetic parameters for both TSs are similar, and dissociation (Kd) or half maximal inhibitory concentration constants (IC50) did not show differential inhibition between the folate analogues. Differences in their amino acid sequence are not reflected in theoretical molecular models of both TSs, since both appear to have identical active sites. These results suggest that the eukaryotic TS active site is very constrained into the functional residues involved in reductive methylation of 2â²-deoxyuridine-5â²-monophosphate (dUMP).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology - Volume 150, Issue 3, September 2009, Pages 406-413
Journal: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology - Volume 150, Issue 3, September 2009, Pages 406-413
نویسندگان
Aldo A. Arvizu-Flores, Emmanuel Aispuro-Hernandez, Karina D. Garcia-Orozco, Alejandro Varela-Romero, Elisa Valenzuela-Soto, Enrique F. Velazquez-Contreras, Arturo Rojo-DomÃnguez, Gloria Yepiz-Plascencia, Frank Maley, Rogerio R. Sotelo-Mundo,