The N-terminus of MTRR plays a role in MTR reactivation cycle beyond electron transfer
| Autor: | Juan Wang, Gui-cen Liu, Shu-qin Wang, Jun Zhang, Mu-hua Jin, Nan-nan Mi, Xiao-lu Dai |
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| Rok vydání: | 2020 |
| Předmět: |
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Molecular Methyltransferase Arginine Protein Conformation Protein domain 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase 01 natural sciences Biochemistry Electron Transport Drug Discovery Humans Amino Acid Sequence Methionine synthase Spinal Dysraphism Molecular Biology Sequence Deletion chemistry.chemical_classification biology 010405 organic chemistry Chemistry Organic Chemistry Exons (Methionine synthase) reductase MTRR 0104 chemical sciences Cell biology Ferredoxin-NADP Reductase N-terminus 010404 medicinal & biomolecular chemistry Enzyme biology.protein Sequence Alignment |
| Zdroj: | Bioorganic Chemistry. 100:103836 |
| ISSN: | 0045-2068 |
| Popis: | In eucaryotic cells, methionine synthase reductase (MSR/MTRR) is capable of dominating the folate-homocysteine metabolism as an irreplaceable partner in electron transfer for regeneration of methionine synthase. The N-terminus of MTRR containing a conserved domain of FMN_Red is closely concerned with the oxidation-reduction process. Maternal substitution of I22M in this domain can bring about pregnancy with high risk of spina bifida. A new variation of Arg2del was identified from a female conceiving a fetus with spina bifida cystica. Although the deletion is far from the N-terminal FMN_Red domain, the biochemical features of the variant had been seriously investigated. Curiously, the deletion of arginine(s) of MTRR could not affect the electron relay, if only the FMN_Red domain was intact, but by degrees reduced the ability to promote MTR catalysis in methionine formation. Confirmation of the interaction between the isolated MTRR N-terminal polypeptide and MTR suggested that the native MTRR N-terminus might play an extra role in MTR function. The tandem arginines at the end of MTRR N-terminus conferring high affinity to MTR were indispensable for stimulating methyltransferase activity perhaps via triggering allosteric effect that could be attenuated by removal of the arginine(s). It was concluded that MTRR could also propel MTR enzymatic reaction relying on the tandem arginines at N-terminus more than just only implicated in electron transfer in MTR reactivation cycle. Perturbance of the enzymatic cooperation due to the novel deletion could possibly invite spina bifida in clinics. |
| Databáze: | OpenAIRE |
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