4OHF

Crystal structure of cytosolic nucleotidase II (LPG0095) in complex with GMP from Legionella pneumophila, NORTHEAST STRUCTURAL GENOMICS CONSORTIUM TARGET LGR1

4OHF の概要

• エントリーDOI: 10.2210/pdb4ohf/pdb
• 関連するPDBエントリー: 4G63
• 分子名称: Cytosolic IMP-GMP specific 5'-nucleotidase, GUANOSINE-5'-MONOPHOSPHATE, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: structural genomics, psi-biology, northeast structural genomics consortium, nesg, 3-domained structure that resembles had, nucleotidase. it catalyzes the breakdown of selected nucleoside monophosphates, cytosol, hydrolase
• 由来する生物種: Legionella pneumophila subsp. pneumophila
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 220505.06

構造登録者

Srinivisan, B.,Forouhar, F.,Shukla, A.,Sampangi, C.,Kulkarni, S.,Abashidze, M.,Seetharaman, J.,Lew, S.,Mao, L.,Acton, T.B.,Xiao, R.,Everett, J.K.,Montelione, G.M.,Tong, L.,Balaram, H.,Northeast Structural Genomics Consortium (NESG) (登録日: 2014-01-17, 公開日: 2014-02-26, 最終更新日: 2023-09-20)

主引用文献

Srinivasan, B.,Forouhar, F.,Shukla, A.,Sampangi, C.,Kulkarni, S.,Abashidze, M.,Seetharaman, J.,Lew, S.,Mao, L.,Acton, T.B.,Xiao, R.,Everett, J.K.,Montelione, G.T.,Tong, L.,Balaram, H.
Allosteric regulation and substrate activation in cytosolic nucleotidase II from Legionella pneumophila.
Febs J., 281:1613-1628, 2014

PubMed Abstract: Cytosolic nucleotidase II (cN-II) from Legionella pneumophila (Lp) catalyzes the hydrolysis of GMP and dGMP displaying sigmoidal curves, whereas catalysis of IMP hydrolysis displayed a biphasic curve in the initial rate versus substrate concentration plots. Allosteric modulators of mammalian cN-II did not activate LpcN-II although GTP, GDP and the substrate GMP were specific activators. Crystal structures of the tetrameric LpcN-II revealed an activator-binding site at the dimer interface. A double mutation in this allosteric-binding site abolished activation, confirming the structural observations. The substrate GMP acting as an activator, partitioning between the allosteric and active site, is the basis for the sigmoidicity of the initial velocity versus GMP concentration plot. The LpcN-II tetramer showed differences in subunit organization upon activator binding that are absent in the activator-bound human cN-II structure. This is the first observation of a structural change induced by activator binding in cN-II that may be the molecular mechanism for enzyme activation.

PubMed: 24456211
DOI: 10.1111/febs.12727

実験手法

X-RAY DIFFRACTION (2.53 Å)