دورية أكاديمية
Crystal and EM structures of human phosphoribosyl pyrophosphate synthase I (PRS1) provide novel insights into the disease-associated mutations.
| العنوان: | Crystal and EM structures of human phosphoribosyl pyrophosphate synthase I (PRS1) provide novel insights into the disease-associated mutations. |
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| المؤلفون: | Peng Chen, Zheng Liu, Xuejuan Wang, Junhui Peng, Qianqian Sun, Jianzhong Li, Mingxing Wang, Liwen Niu, Zhiyong Zhang, Gang Cai, Maikun Teng, Xu Li |
| المصدر: | PLoS ONE, Vol 10, Iss 3, p e0120304 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Human PRS1, which is indispensable for the biosynthesis of nucleotides, deoxynucleotides and their derivatives, is associated directly with multiple human diseases because of single base mutation. However, a molecular understanding of the effect of these mutations is hampered by the lack of understanding of its catalytic mechanism. Here, we reconstruct the 3D EM structure of the PRS1 apo state. Together with the native stain EM structures of AMPNPP, AMPNPP and R5P, ADP and the apo states with distinct conformations, we suggest the hexamer is the enzymatically active form. Based on crystal structures, sequence analysis, mutagenesis, enzyme kinetics assays, and MD simulations, we reveal the conserved substrates binding motifs and make further analysis of all pathogenic mutants. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0120304 |
| URL الوصول: | https://doaj.org/article/3c8bfd7546e64c6492dd8b3b75ee46c5 |
| رقم الأكسشن: | edsdoj.3c8bfd7546e64c6492dd8b3b75ee46c5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0120304 |