2018
DOI: 10.7554/elife.37373
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Evolution of cation binding in the active sites of P-loop nucleoside triphosphatases in relation to the basic catalytic mechanism

Abstract: The ubiquitous P-loop fold nucleoside triphosphatases (NTPases) are typically activated by an arginine or lysine ‘finger’. Some of the apparently ancestral NTPases are, instead, activated by potassium ions. To clarify the activation mechanism, we combined comparative structure analysis with molecular dynamics (MD) simulations of Mg-ATP and Mg-GTP complexes in water and in the presence of potassium, sodium, or ammonium ions. In all analyzed structures of diverse P-loop NTPases, the conserved P-loop motif keeps … Show more

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Cited by 38 publications
(113 citation statements)
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References 138 publications
(252 reference statements)
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“…In the GMPPCP‐bound K56A Vps1 GTPase‐BSE structure, we observed weak density centered on the position where the ε‐amino group of the P‐loop lysine is located in the Vps1 GTPase‐BSE structure in one of the 4 molecules in the asymmetric unit, which we interpreted as a poorly‐ordered water. A function of the P‐loop is to keep the phosphates in the GTP in an extended conformation to permit hydrolysis . Molecular dynamics simulations show that, in water, Mg 2+ ‐ATP or Mg 2+ ‐GTP are held in an equivalent extended conformation by K + , Na + or NH 4 + ions.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…In the GMPPCP‐bound K56A Vps1 GTPase‐BSE structure, we observed weak density centered on the position where the ε‐amino group of the P‐loop lysine is located in the Vps1 GTPase‐BSE structure in one of the 4 molecules in the asymmetric unit, which we interpreted as a poorly‐ordered water. A function of the P‐loop is to keep the phosphates in the GTP in an extended conformation to permit hydrolysis . Molecular dynamics simulations show that, in water, Mg 2+ ‐ATP or Mg 2+ ‐GTP are held in an equivalent extended conformation by K + , Na + or NH 4 + ions.…”
Section: Resultsmentioning
confidence: 99%
“…Molecular dynamics simulations show that, in water, Mg 2+ ‐ATP or Mg 2+ ‐GTP are held in an equivalent extended conformation by K + , Na + or NH 4 + ions. In an active site, the ε‐amino group of the P‐loop lysine is in the same position as one of the ions (the other is either an ion or an arginine/lysine) . We therefore hypothesized that, if the weak density is an ion, the effects of the loss of the positive charge contributed by the lysine may be counteracted by increasing the concentration of cations available to the active site.…”
Section: Resultsmentioning
confidence: 99%
“…206S is also relatively deshielded ( δ =9.4 ppm) for DnaB:ADP:AlF 4 − :DNA. The equivalent residue to 206S has been identified in other NTPases, whose structures locate this residue in the Walker A motif near the fluorine atom of the γ‐phosphate mimic, identifying its key role in stabilizing the γ phosphate during ATP hydrolysis …”
Section: Figurementioning
confidence: 99%
“…This implies that the MnmEG complex must discriminate against a variety of uridine residues located within RNA loops. This discrimination is performed by the potassium‐dependent GTPase activity of subunit E of the complex (Fislage et al , 2016; Shalaeva et al , 2018; Boel et al , 2019; Danchin and Nikel, 2019; Gao et al , 2019). Remarkably, this subunit also regulates the activity of the H 4 F‐related enzyme, poly‐γ‐glutamyl H 2 F/H 4 F synthase FolC, discussed at the beginning of this article.…”
Section: Folate‐dependent Modification Of Rnas and Proteinsmentioning
confidence: 99%
“…However, while the modifications were likely important for proper integration of metabolism, they did not usually have a significant effect on the growth rate of E. coli strains in standard growth conditions. In contrast, when the host strain was deficient in the synthesis of polyamines, deletion of the mnmE or mnmG gene resulted in complete inhibition of growth unless the medium contained polyamines (Rodionova et al , 2018; Shalaeva et al , 2018; Gao et al , 2019; Keller et al , 2019).…”
Section: Folate‐dependent Modification Of Rnas and Proteinsmentioning
confidence: 99%