1.9 A structure of the signal receiver domain of the putative response regulator NarL from Mycobacterium tuberculosis - PubMed (original) (raw)

Comparative Study

. 2008 Dec 1;64(Pt 12):1096-100.

doi: 10.1107/S1744309108035203. Epub 2008 Nov 28.

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Comparative Study

1.9 A structure of the signal receiver domain of the putative response regulator NarL from Mycobacterium tuberculosis

Robert Schnell et al. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008.

Abstract

NarL from Mycobacterium tuberculosis is a putative nitrate response regulator that is involved in the regulation of anaerobic metabolism in this pathogen. The recombinant purified N-terminal signal receiver domain of NarL has been crystallized in space group C222(1), with unit-cell parameters a = 85.6, b = 90.0, c = 126.3 A, and the structure was determined by molecular replacement to 1.9 A resolution. Comparisons with related signal receiver domains show that the closest structural homologue is an uncharacterized protein from Staphylococcus aureus, whereas the nearest sequence homologue, NarL from Escherichia coli, displays larger differences in three-dimensional structure. The largest differences between the mycobacterial and E. coli NarL domains were found in the loop between beta3 and alpha3 in the proximity of the phosphorylation site. The active site in response regulators is similar to that of members of the haloacid dehalogenase (HAD) family, which also form a phospho-aspartyl intermediate. In NarL, the aspartic acid that acts as catalytic acid/base in several HAD enzymes is replaced by an arginine residue, which is less likely to participate in steps involving proton abstraction. This substitution may slow down the breakdown of the phospho-aspartyl anhydride and allow signalling beyond the timescales defined by a catalytic reaction intermediate.

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Figures

Figure 1

Figure 1

(a) Part of the unbiased 2_F_ o − F c map illustrating the difference density for the fourth molecule (monomer D) in the asymmetric unit. The electron-density map was ob­tained after locating molecules A, B and C by molecular replacement and refinement using only these three mole­cules. The refined structure of part of molecule D is included. (b) Cartoon of the overall structure of the signal receiver domain of NarL from M. tuberculosis. Helices are shown in blue and β-strands in brown. The side chain of Asp61, the site of phosphorylation, is indicated as a stick model. (c) Superposition of the Cα traces of the N-terminal signal receiver domains of NarL from M. tuberculosis (blue) and E. coli (green). The side chain of Asp61, the site of phosphorylation, is indicated as a stick model. (d) Com­parison of the phosphorylation site in NarL from M. tuberculosis (standard colours) with the active site of histidinol phosphate phosphatase from E. coli (PDB code

2fpw

; blue lines). The active site of the histidinol phosphate phosphatase contains a phosphorylated reaction intermediate, the phosphoryl–aspartic acid mixed anhydride formed at position Asp57, and a Ca2+ ion (indicated by a green sphere) replacing the catalytic Mg2+ ion.

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