6OFB

Crystal structure of human glutamine-dependent NAD+ synthetase complexed with NaAD+, AMP, pyrophosphate, and Mg2+

6OFB の概要

• エントリーDOI: 10.2210/pdb6ofb/pdb
• 関連するPDBエントリー: 6OFC
• 分子名称: Glutamine-dependent NAD(+) synthetase, NICOTINIC ACID ADENINE DINUCLEOTIDE, ADENOSINE MONOPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: ligase, glutamine-amido transferase, gat, nad+ synthetase, glutamine-dependent nad+ synthetase, nad synthetase 1, glutaminase, ammonia tunneling, enzyme, atp-binding, nucleotide-binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 161708.32

構造登録者

Chuenchor, W.,Doukov, T.I.,Gerratana, B. (登録日: 2019-03-28, 公開日: 2020-01-08, 最終更新日: 2023-10-25)

主引用文献

Chuenchor, W.,Doukov, T.I.,Chang, K.T.,Resto, M.,Yun, C.S.,Gerratana, B.
Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+synthetases.
Nat Commun, 11:16-16, 2020

PubMed Abstract: NAD synthetase is an essential enzyme of de novo and recycling pathways of NAD biosynthesis in Mycobacterium tuberculosis but not in humans. This bifunctional enzyme couples the NAD synthetase and glutaminase activities through an ammonia tunnel but free ammonia is also a substrate. Here we show that the Homo sapiens NAD synthetase (hsNadE) lacks substrate specificity for glutamine over ammonia and displays a modest activation of the glutaminase domain compared to tbNadE. We report the crystal structures of hsNadE and NAD synthetase from M. tuberculosis (tbNadE) with synthetase intermediate analogues. Based on the observed exclusive arrangements of the domains and of the intra- or inter-subunit tunnels we propose a model for the inter-domain communication mechanism for the regulation of glutamine-dependent activity and NH transport. The structural and mechanistic comparison herein reported between hsNadE and tbNadE provides also a starting point for future efforts in the development of anti-TB drugs.

PubMed: 31911602
DOI: 10.1038/s41467-019-13845-4

実験手法

X-RAY DIFFRACTION (2.84 Å)