The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase - PubMed (original) (raw)
The first step of aminoacylation at the atomic level in histidyl-tRNA synthetase
J G Arnez et al. Proc Natl Acad Sci U S A. 1997.
Abstract
The crystal structure of an enzyme-substrate complex with histidyl-tRNA synthetase from Escherichia coli, ATP, and the amino acid analog histidinol is described and compared with the previously obtained enzyme-product complex with histidyl-adenylate. An active site arginine, Arg-259, unique to all histidyl-tRNA synthetases, plays the role of the catalytic magnesium ion seen in seryl-tRNA synthetase. When Arg-259 is substituted with histidine, the apparent second order rate constant (kcat/Km) for the pyrophosphate exchange reaction and the aminoacylation reaction decreases 1,000-fold and 500-fold, respectively. Crystals soaked with MnCl2 reveal the existence of two metal binding sites between beta- and gamma-phosphates; these sites appear to stabilize the conformation of the pyrophosphate. The use of both conserved metal ions and arginine in phosphoryl transfer provides evidence of significant early functional divergence of class II aminoacyl-tRNA synthetases.
Figures
Figure 1
Stereoviews of superpositions of the histidinol:ATP (blue bonds) and histidyl-adenylate (red bonds) complexes (a), and the ATPs from the HisRS:histidinol:ATP complex (red) and yeast AspRS:tRNA:ATP complex (blue) (b). The figure was prepared by using
molscript
(27) and
raster3d
(28, 29).
Figure 2
Stereoviews of electron density maps of ligands in the active site of HisRS. Final 2_F_o − _F_c map contoured at 1σ of the active site of the HisRS:HisOH:ATP complex (a) and HisRS:HisAMP complex (b), superposed on the final refined structures. (c) HisRS:HisOH:ATP:Mn2+ complex. An _F_o − _F_c map contoured at 4.5 σ (red); the map was computed with structure factors and phases calculated from the model in a. The figure was prepared by using
minimage
(30),
molscript
(27), and
raster3d
(28, 29).
Figure 3
Schematic diagram showing steps in the activation of histidine by HisRS: (a) binding of histidinol and ATP, (b) proposed transition state with pentavalent α-phosphate, and (c) formation of histidyl-adenylate (14). a and c are based on crystallographic data, whereas b is a proposed model for the transition state.
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