1CE8

CARBAMOYL PHOSPHATE SYNTHETASE FROM ESCHERICHIS COLI WITH COMPLEXED WITH THE ALLOSTERIC LIGAND IMP

1CE8 の概要

• エントリーDOI: 10.2210/pdb1ce8/pdb
• 分子名称: PROTEIN (CARBAMOYL-PHOSPHATE SYNTHASE), TETRAETHYLAMMONIUM ION, MANGANESE (II) ION, ... (11 entities in total)
• 機能のキーワード: imp, allosteric ligand, ligase imp
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 646802.38

構造登録者

Thoden, J.B.,Raushel, F.M.,Holden, H.M. (登録日: 1999-03-18, 公開日: 1999-07-26, 最終更新日: 2023-09-20)

主引用文献

Thoden, J.B.,Raushel, F.M.,Wesenberg, G.,Holden, H.M.
The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase.
J.Biol.Chem., 274:22502-22507, 1999

PubMed Abstract: Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate, which is subsequently employed in both the pyrimidine and arginine biosynthetic pathways. The reaction mechanism is known to proceed through at least three highly reactive intermediates: ammonia, carboxyphosphate, and carbamate. In keeping with the fact that the product of CPS is utilized in two competing metabolic pathways, the enzyme is highly regulated by a variety of effector molecules including potassium and ornithine, which function as activators, and UMP, which acts as an inhibitor. IMP is also known to bind to CPS but the actual effect of this ligand on the activity of the enzyme is dependent upon both temperature and assay conditions. Here we describe the three-dimensional architecture of CPS with bound IMP determined and refined to 2.1 A resolution. The nucleotide is situated at the C-terminal portion of a five-stranded parallel beta-sheet in the allosteric domain formed by Ser(937) to Lys(1073). Those amino acid side chains responsible for anchoring the nucleotide to the polypeptide chain include Lys(954), Thr(974), Thr(977), Lys(993), Asn(1015), and Thr(1017). A series of hydrogen bonds connect the IMP-binding pocket to the active site of the large subunit known to function in the phosphorylation of the unstable intermediate, carbamate. This structural analysis reveals, for the first time, the detailed manner in which CPS accommodates nucleotide monophosphate effector molecules within the allosteric domain.

PubMed: 10428826
DOI: 10.1074/jbc.274.32.22502

実験手法

X-RAY DIFFRACTION (2.1 Å)