4G63

Crystal structure of cytosolic IMP-GMP specific 5'-nucleotidase (lpg0095) in complex with phosphate ions from Legionella pneumophila, Northeast Structural Genomics Consortium Target LgR1

Summary for 4G63

• Entry DOI: 10.2210/pdb4g63/pdb
• Related: 2BDE
• Descriptor: Cytosolic IMP-GMP specific 5'-nucleotidase, PHOSPHATE ION (3 entities in total)
• Functional Keywords: structural genomics, psi-biology, northeast structural genomics consortium, nesg, alpha-beta protein, had-like superfamily, dna binding protein
• Biological source: Legionella pneumophila subsp. pneumophila
• Total number of polymer chains: 1
• Total formula weight: 54926.43

Authors

Forouhar, F.,Abashidze, M.,Seetharaman, J.,Ho, C.K.,Ciccosanti, C.,Mao, L.,Xiao, R.,Acton, T.B.,Montelione, G.T.,Tong, L.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2012-07-18, release date: 2012-10-10, Last modification date: 2023-09-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)