4KH1

The R state structure of E. coli ATCase with CTP,UTP, and Magnesium bound

4KH1 の概要

• エントリーDOI: 10.2210/pdb4kh1/pdb
• 関連するPDBエントリー: 4KGV 4KGX 4KGZ 4KH0
• 分子名称: Aspartate carbamoyltransferase, Aspartate carbamoyltransferase regulatory chain, N-(PHOSPHONACETYL)-L-ASPARTIC ACID, ... (9 entities in total)
• 機能のキーワード: pyrimidine nucleotide biosynthesis, feedback inhibition, competing pathway product activation, allostery, transferase
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 105680.69

構造登録者

Cockrell, G.M.,Zheng, Y.,Guo, W.,Peterson, A.W.,Kantrowitz, E.R. (登録日: 2013-04-29, 公開日: 2013-11-27, 最終更新日: 2023-09-20)

主引用文献

Cockrell, G.M.,Zheng, Y.,Guo, W.,Peterson, A.W.,Truong, J.K.,Kantrowitz, E.R.
New Paradigm for Allosteric Regulation of Escherichia coli Aspartate Transcarbamoylase.
Biochemistry, 52:8036-8047, 2013

PubMed Abstract: For nearly 60 years, the ATP activation and the CTP inhibition of Escherichia coli aspartate transcarbamoylase (ATCase) has been the textbook example of allosteric regulation. We present kinetic data and five X-ray structures determined in the absence and presence of a Mg(2+) concentration within the physiological range. In the presence of 2 mM divalent cations (Mg(2+), Ca(2+), Zn(2+)), CTP does not significantly inhibit the enzyme, while the allosteric activation by ATP is enhanced. The data suggest that the actual allosteric inhibitor of ATCase in vivo is the combination of CTP, UTP, and a divalent cation, and the actual allosteric activator is a divalent cation with ATP or ATP and GTP. The structural data reveals that two NTPs can bind to each allosteric site with a divalent cation acting as a bridge between the triphosphates. Thus, the regulation of ATCase is far more complex than previously believed and calls many previous studies into question. The X-ray structures reveal that the catalytic chains undergo essentially no alternations; however, several regions of the regulatory chains undergo significant structural changes. Most significant is that the N-terminal region of the regulatory chains exists in different conformations in the allosterically activated and inhibited forms of the enzyme. Here, a new model of allosteric regulation is proposed.

PubMed: 24138583
DOI: 10.1021/bi401205n

実験手法

X-RAY DIFFRACTION (2.2 Å)