5Z83

Crystal structure of GenB1 from Micromonospora echinospora in complex with PLP (internal aldimine)

5Z83 の概要

• エントリーDOI: 10.2210/pdb5z83/pdb
• 分子名称: C-6' aminotransferase, PYRIDOXAL-5'-PHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: aminotransferase, transferase
• 由来する生物種: Micromonospora echinospora (Micromonospora purpurea)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94891.71

構造登録者

Hong, S.K.,Cha, S.S. (登録日: 2018-01-30, 公開日: 2019-01-16, 最終更新日: 2019-02-27)

主引用文献

Ban, Y.H.,Song, M.C.,Hwang, J.Y.,Shin, H.L.,Kim, H.J.,Hong, S.K.,Lee, N.J.,Park, J.W.,Cha, S.S.,Liu, H.W.,Yoon, Y.J.
Complete reconstitution of the diverse pathways of gentamicin B biosynthesis.
Nat. Chem. Biol., 15:295-303, 2019

PubMed Abstract: Gentamicin B (GB), a valuable starting material for the preparation of the semisynthetic aminoglycoside antibiotic isepamicin, is produced in trace amounts by the wild-type Micromonospora echinospora. Though the biosynthetic pathway to GB has remained obscure for decades, we have now identified three hidden pathways to GB production via seven hitherto unknown intermediates in M. echinospora. The narrow substrate specificity of a key glycosyltransferase and the C6'-amination enzymes, in combination with the weak and unsynchronized gene expression of the 2'-deamination enzymes, limits GB production in M. echinospora. The crystal structure of the aminotransferase involved in C6'-amination explains its substrate specificity. Some of the new intermediates displayed similar premature termination codon readthrough activity but with reduced toxicity compared to the natural aminoglycoside G418. This work not only led to the discovery of unknown biosynthetic routes to GB, but also demonstrated the potential to mine new aminoglycosides from nature for drug discovery.

PubMed: 30643280
DOI: 10.1038/s41589-018-0203-4

実験手法

X-RAY DIFFRACTION (1.7 Å)