Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2473
Title: Allosteric regulation and substrate activation in cytosolic nucleotidase II from Legionella pneumophila
Authors: Srinivasan, Bharath
Forouhar, Farhad
Shukla, Arpit
Sampangi, Chethana
Kulkarni, Sonia
Abashidze, Mariam
Seetharaman, Jayaraman
Lew, Scott
Mao, Lei
Acton, Thomas B.
Xiao, Rong
Everett, John K.
Montelione, Gaetano T.
Tong, Liang
Balaram, Hemalatha
Keywords: Biochemistry & Molecular Biology
5-Nucleotidase
Allostery
Gmp-Complexed LPCN-Ii Structure
Heterotropic Activation
Substrate Activation
IMP-GMP 5'-Nucleotidase
Glycerate 2,3-Bisphosphate
Molecular Replacement
Sequence Alignment
HAD Superfamily
Rat-Brain
5-Nucleotidase
Metabolism
Program
ATP
Issue Date: 2014
Publisher: Wiley-Blackwell
Citation: Srinivasan, B; Forouhar, F; Shukla, A; Sampangi, C; Kulkarni, S; Abashidze, M; Seetharaman, J; Lew, S; Mao, L; Acton, TB; Xiao, R; Everett, JK; Montelione, GT; Tong, L; Balaram, H, Allosteric regulation and substrate activation in cytosolic nucleotidase II from Legionella pneumophila. Febs Journal 2014, 281 (6) 1613-1628, http://dx.doi.org/10.1111/febs.12727
FEBS Journal
281
6
Abstract: Cytosolic nucleotidase II (cN-II) from Legionellapneumophila (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. DatabaseThe coordinates and structure factors reported in this paper have been submitted to the Protein Data Bank under the accession numbers and . The accession number of GMP complexed LpcN-II is . Structured digital abstract <list list-type="bulleted" id="febs12727-list-0001"> andby() andby() [Structured digital abstract was added on 5 March 2014 after original online publication]
Description: Restricted Access
URI: http://hdl.handle.net/10572/2473
ISSN: 1742-464X
Appears in Collections:Research Papers (Hemalatha Balaram)

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