التفاصيل البيبلوغرافية
| العنوان: |
Structural studies reveal flexible roof of active site responsible for ω-transaminase CrmG overcoming by-product inhibition. |
| المؤلفون: |
Xu, Jinxin, Tang, Xiaowen, Zhu, Yiguang, Yu, Zhijun, Su, Kai, Zhang, Yulong, Dong, Yan, Zhu, Weiming, Zhang, Changsheng, Wu, Ruibo, Liu, Jinsong |
| المصدر: |
Communications Biology; 8/19/2020, Vol. 3 Issue 1, pN.PAG-N.PAG, 1p |
| مصطلحات موضوعية: |
AMINOTRANSFERASES, AMINES, BIOSYNTHESIS, PYRUVATES, CATALYSIS |
| مستخلص: |
Amine compounds biosynthesis using ω-transaminases has received considerable attention in the pharmaceutical industry. However, the application of ω-transaminases was hampered by the fundamental challenge of severe by-product inhibition. Here, we report that ω-transaminase CrmG from Actinoalloteichus cyanogriseus WH1-2216-6 is insensitive to inhibition from by-product α-ketoglutarate or pyruvate. Combined with structural and QM/MM studies, we establish the detailed catalytic mechanism for CrmG. Our structural and biochemical studies reveal that the roof of the active site in PMP-bound CrmG is flexible, which will facilitate the PMP or by-product to dissociate from PMP-bound CrmG. Our results also show that amino acceptor caerulomycin M (CRM M), but not α-ketoglutarate or pyruvate, can form strong interactions with the roof of the active site in PMP-bound CrmG. Based on our results, we propose that the flexible roof of the active site in PMP-bound CrmG may facilitate CrmG to overcome inhibition from the by-product. Xu, Tang et al. show that ω-transaminase CrmG is insensitive to the inhibition from by-products α-ketoglutarate or pyruvate. They find that these by-products cannot interact strongly with the flexible roof of the active site in CrmG. This study provides insights into the rational design of transaminase to eliminate by-product inhibition. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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