4WIO

Crystal structure of the C89A GMP synthetase inactive mutant from Plasmodium falciparum in complex with glutamine

4WIO の概要

• エントリーDOI: 10.2210/pdb4wio/pdb
• 関連するPDBエントリー: 4WIM 4WIN
• 分子名称: GMP synthetase, GLUTAMINE (3 entities in total)
• 機能のキーワード: gmp synthetase, purine salvage pathway, ligase
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 65458.51

構造登録者

Ballut, L.,Violot, S.,Haser, R.,Aghajari, N. (登録日: 2014-09-26, 公開日: 2015-12-02, 最終更新日: 2024-10-23)

主引用文献

Ballut, L.,Violot, S.,Shivakumaraswamy, S.,Thota, L.P.,Sathya, M.,Kunala, J.,Dijkstra, B.W.,Terreux, R.,Haser, R.,Balaram, H.,Aghajari, N.
Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation.
Nat Commun, 6:8930-8930, 2015

PubMed Abstract: GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85° rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371-375 holding catalytic residues and in loop 376-401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.

PubMed: 26592566
DOI: 10.1038/ncomms9930

実験手法

X-RAY DIFFRACTION (3.15 Å)