4OHF: Crystal Structure Of Cytosolic Nucleotidase Ii (lpg0095) In Complex With Gmp From Legionella Pneumophila, Northeast Structural Genomics Consortium Target Lgr1

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. DATABASE: The coordinates and structure factors reported in this paper have been submitted to the Protein Data Bank under the accession numbers 2BDE and 4G63. The accession number of GMP complexed LpcN-II is 4OHF. STRUCTURED DIGITAL ABSTRACT: LpcN-II and LpcN-II bind by molecular sieving (View interaction) LpcN-II and LpcN-II bind by x-ray crystallography (View interaction) [Structured digital abstract was added on 5 March 2014 after original online publication].
PDB ID: 4OHFDownload
MMDB ID: 117883
PDB Deposition Date: 2014/1/17
Updated in MMDB: 2014/04
Experimental Method:
x-ray diffraction
Resolution: 2.53  Å
Source Organism:
Similar Structures:
Biological Unit for 4OHF: tetrameric; determined by author
Molecular Components in 4OHF
Label Count Molecule
Proteins (4 molecules)
Cytosolic Imp-gmp Specific 5'-nucleotidase
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB