کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9140163 | 1163399 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Subunit complementation of thymidylate synthase in Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase
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کلمات کلیدی
H2folateDeoxythymidine 5′-monophosphateDTMPLactobacillus caseiFdUMPDHFR-TSdihydrofolate reductase-thymidylate synthase5,10-Methylenetetrahydrofolate - 5،10-متیلن تترا هیدرو فولات7,8-dihydrofolate - 7،8-دی هیدرو فولاتdhfr - DhfrSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدSodium dodecyl sulfate polyacrylamide gel electrophoresis - الکتروفورز ژل پلی اتیل آمید سدیم دودسیل سولفاتOligonucleotide - اولیگونوکلئوتیدdihydrofolate reductase - دی هیدروفلات ردوکتازdUMP - زبالهthymidylate synthase - سمیاتید تیمیدیلاتMalaria - مالاریاpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازPlasmodium falciparum - پلاسمودیوم فالسیپاروم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Subunit complementation of thymidylate synthase in Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Subunit complementation of thymidylate synthase in Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase](/preview/png/9140163.png)
چکیده انگلیسی
Thymidylate synthase of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) functions as a dimeric enzyme with extensive contact between the two TS domains. Structural data of PfDHFR-TS shows that the formation of the two TS active sites involves contribution of the amino acid residues from both TS domains. Arg-470 donated from the adjoining domain is shown to hydrogen-bond to dUMP, while Cys-490 is a key nucleophile for TS catalysis by attacking C-6 of dUMP. However, mutants of the two series could complement one another, giving rise to active enzyme. By means of subunit complementation assay using Arg-470 and Cys-490 mutants, it is shown that co-transformants of both TS-inactive Arg-470 and Cys-490 mutants can complement the growth of thymidine auxotroph Ï2913RecA(DE3) by formation of a functional TS heterodimer contributing from both Arg-470 and Cys-490 mutant subunits. 6-[3H]-FdUMP thymidylate synthase activity assay further elaborate the essence of restoration of TS activity. The TS kcat value of the R470DÂ +Â C490A heterodimer is decreased by half from that of the wild-type PfDHFR-TS. However, the Km values for dUMP and CH2H4folate of the R470DÂ +Â C490A heterodimer are similar to those of wild-type enzyme, indicating that the catalytic efficiency of the functional TS from the R470DÂ +Â C490A heterodimer is similar to the wild-type TS enzyme in P. falciparum DHFR-TS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Biochemical Parasitology - Volume 139, Issue 1, January 2005, Pages 83-90
Journal: Molecular and Biochemical Parasitology - Volume 139, Issue 1, January 2005, Pages 83-90
نویسندگان
Manee Chanama, Penchit Chitnumsub, Yongyuth Yuthavong,