6H78

E1 enzyme for ubiquitin like protein activation.

6H78 の概要

• エントリーDOI: 10.2210/pdb6h78/pdb
• 分子名称: Ubiquitin-like modifier-activating enzyme 5, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: ubiquitin like protein activating enzyme, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 545129.19

構造登録者

Soudah, N.,Padala, P.,Hassouna, F.,Mashahreh, B.,Lebedev, A.A.,Isupov, M.N.,Cohen-Kfir, E.,Wiener, R. (登録日: 2018-07-30, 公開日: 2018-10-31, 最終更新日: 2024-01-17)

主引用文献

Soudah, N.,Padala, P.,Hassouna, F.,Kumar, M.,Mashahreh, B.,Lebedev, A.A.,Isupov, M.N.,Cohen-Kfir, E.,Wiener, R.
An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation.
J.Mol.Biol., 431:463-478, 2019

PubMed Abstract: Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1-activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1.

PubMed: 30412706
DOI: 10.1016/j.jmb.2018.10.007

実験手法

X-RAY DIFFRACTION (2.7 Å)