6D9Q

The sulfate-bound crystal structure of HPRT (hypoxanthine phosphoribosyltransferase)

6D9Q の概要

• エントリーDOI: 10.2210/pdb6d9q/pdb
• 関連するPDBエントリー: 3H83 3KB8
• 分子名称: Hypoxanthine phosphoribosyltransferase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: hprt, hypoxanthine phosphoribosyltransferase, transferase
• 由来する生物種: Bacillus anthracis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82875.18

構造登録者

Satyshur, K.A.,Dubiel, K.,Anderson, B.,Wolak, C.,Keck, J.L. (登録日: 2018-04-30, 公開日: 2019-05-01, 最終更新日: 2023-10-04)

主引用文献

Anderson, B.W.,Liu, K.,Wolak, C.,Dubiel, K.,She, F.,Satyshur, K.A.,Keck, J.L.,Wang, J.D.
Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction.
Elife, 8:-, 2019

PubMed Abstract: The alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal (p)ppGpp inhibits the purine salvage enzyme HPRT by sharing a conserved motif with its substrate PRPP. Intriguingly, HPRT regulation by (p)ppGpp varies across organisms and correlates with HPRT oligomeric forms. (p)ppGpp-sensitive HPRT exists as a PRPP-bound dimer or an apo- and (p)ppGpp-bound tetramer, where a dimer-dimer interface triggers allosteric structural rearrangements to enhance (p)ppGpp inhibition. Loss of this oligomeric interface results in weakened (p)ppGpp regulation. Our results reveal an evolutionary principle whereby protein oligomerization allows evolutionary change to accumulate away from a conserved binding pocket to allosterically alter specificity of ligand interaction. This principle also explains how another (p)ppGpp target GMK is variably regulated across species. Since most ligands bind near protein interfaces, we propose that this principle extends to many other protein-ligand interactions.

PubMed: 31552824
DOI: 10.7554/eLife.47534

実験手法

X-RAY DIFFRACTION (2.056 Å)