کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5504316 1536275 2017 36 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Human and Plasmodium serine hydroxymethyltransferases differ in rate-limiting steps and pH-dependent substrate inhibition behavior
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Human and Plasmodium serine hydroxymethyltransferases differ in rate-limiting steps and pH-dependent substrate inhibition behavior
چکیده انگلیسی
Serine hydroxymethyltransferase (SHMT), an essential enzyme for cell growth and development, catalyzes the transfer of -CH2OH from l-serine to tetrahydrofolate (THF) to form glycine and 5,10-methylenetetrahydrofolate (MTHF) which is used for nucleotide synthesis. Insights into the ligand binding and inhibition properties of human cytosolic SHMT (hcSHMT) and Plasmodium SHMT (PvSHMT) are crucial for designing specific drugs against malaria and cancer. The results presented here revealed strong and pH-dependent THF inhibition of hcSHMT. In contrast, in PvSHMT, THF inhibition and the influence of pH were not as pronounced. Ligand binding experiments performed at various pH values indicated that the hcSHMT:Gly complex binds THF more tightly at lower pH conditions, while the binding affinity of the PvSHMT:Gly complex for THF is not pH-dependent. Pre-steady state kinetic (rapid-quench) analysis of hcSHMT showed burst kinetics, indicating that glycine formation occurs fastest in the first turnover relative to the subsequent turnovers i.e. glycine release is the rate-limiting step in the hcSHMT reaction. All data suggest that excess THF likely binds E:Gly binary complex and forms the E:Gly:THF dead-end complex before glycine is released. A unique flap motif found in the structure of hcSHMT may be the key structural feature that imparts these described characteristics of hcSHMT.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 630, 15 September 2017, Pages 91-100
نویسندگان
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