A Distinct Motif in a Prokaryotic Small Ras-Like GTPase Highlights Unifying Features of Walker B Motifs in P-Loop NTPases

Kanade, Manil; Chakraborty, Sukanya; Shelke, Sanket Satish; Gayathri, P.

doi:10.1016/j.jmb.2020.07.024

Cited by 15 publications

(33 citation statements)

References 49 publications

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“…1B, other strictly conserved ligands are O 2B and O 1G atoms of the triphosphate chain as ligands #1 and #2, respectively, and water molecules as ligands #5 (W5) and #6 (W6). The position #3 is taken either by water W3 or by diverse amino acid residues in different enzyme families, see [32] for details. The positions of Mg 2+ ligands are similar over the entire superfamily of P-loop NTPases.…”

Section: Coordination Of the Mg-triphosphate Moietymentioning

confidence: 99%

“…In small P-loop NTPases, the titular p hosphate-binding loop (P-loop) usually connects the first β-strand (β 1 -strand) with the first α-helix (α 1 -helix); the P-loop together with the two first residues of the α 1 -helix have the [G/A]xxxxGK[S/T] sequence, known as the Walker A motif [1]. This motif is responsible for the binding of the triphosphate chain and cofactor Mg 2+ ion, see [1, 2, 32] and Fig. 1A-D.…”

Section: Introductionmentioning

confidence: 99%

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Common mechanism of activated catalysis in P-loop fold nucleoside triphosphatases -in varietate concordia

Kozlova

Shalaeva

Dibrova

2022

Preprint

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Although P-loop fold nucleoside triphosphatases (also known as Walker NTPases) are ubiquitous, their catalytic mechanism remains obscure. Based on a comparative structural analysis of 3136 Mg-NTP-containing catalytic sites, we propose a common scheme of activated catalysis for P-loop NTPases where a hydrogen bond (H-bond) between the strictly conserved, Mg-coordinating Ser/Thr of the Walker A motif ([Ser/Thr]WA) and the conserved aspartate of the Walker B motif (AspWB) plays the key role. We found that this H-bond is very short in the structures with bound transition state (TS) analogs. We suggest that the proton affinities of these two residues reverse in the TS so that the proton relocates from [Ser/Thr]WA to AspWB. The anionic [Ser/Thr]WA withdraws then a proton from the (catalytic) water molecule, and the nascent hydroxyl anion attacks gamma-phosphate. When the gamma-phosphate group breaks away, the trapped proton relays from AspWB, via [Ser/Thr]WA, to beta-phosphate and compensates for its developing negative charge.

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Section: Coordination Of the Mg-triphosphate Moietymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Common mechanism of activated catalysis in P-loop fold nucleoside triphosphatases -in varietate concordia

Kozlova

Shalaeva

Dibrova

2022

Preprint

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“…Rather, the canonical Asp at the tip of β2 ligates a catalytic dication ( Figure 2C). Further, tubulin's binding of the dication adopts a P-loop-like octahedral geometry 29 , with both the β2-Asp of tubulin and the Walker B-Asp of P-loops interacting with water molecules that occupy equivalent coordination sites (Figure 2-figure supplement 3). The β2-Asp is essential for tubulin's catalytic activity 30…”

Section: Tubulin -A Parallelly Evolved Rossmann Ntpasementioning

confidence: 99%

On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment

Longo

Jabłońska

Vyas

et al. 2020

eLife

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127

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This article is dedicated to the memory of Michael G. Rossmann. Dating back to the last universal common ancestor, P-loop NTPases and Rossmanns comprise the most ubiquitous and diverse enzyme lineages. Despite similarities in their overall architecture and phosphate binding motif, a lack of sequence identity and some fundamental structural differences currently designates them as independent emergences. We systematically searched for structure and sequence elements shared by both lineages. We detected homologous segments that span the first βαβ motif of both lineages, including the phosphate binding loop and a conserved aspartate at the tip of β2. The latter ligates the catalytic metal in P-loop NTPases, while in Rossmanns it binds the nucleotide’s ribose moiety. Tubulin, a Rossmann GTPase, demonstrates the potential of the β2-Asp to take either one of these two roles. While convergence cannot be completely ruled out, we show that both lineages likely emerged from a common βαβ segment that comprises the core of these enzyme families to this very day.

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“…In P-loop NTPases, the eponymous P-loop, together with the first two residues of the following α-helix, usually follows the sequence pattern [G/A]xxxxGK[S/T], known as the Walker A motif [1]. This motif is stabilizing the triphosphate chain of NTP and the cofactor Mg 2+ ion, see [1, 2, 24] and Fig. 1A-D.…”

Section: Introductionmentioning

confidence: 99%

“…The Walker B motif hhhh[D/E], where “h” denotes a hydrophobic residue, is the other common motif of P-loop NTPases that is found on the C-terminal tip of that β-strand, which is opposite the Walker A α-helix, see Fig. 1A,B and [1, 2, 24]. The conserved Asp/Glu residue of the Walker B motif links it with the last [S/T] residue of the Walker A motif by a hydrogen bond (H-bond), see Fig.…”

Section: Introductionmentioning

confidence: 99%

Common patterns of hydrolysis initiation in P-loop fold nucleoside triphosphatases

Kozlova

Shalaeva

Dibrova

2022

Preprint

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In ubiquitous P-loop fold nucleoside triphosphatases (also known as Walker NTPases), hydrolysis of ATP or GTP is triggered by interaction with an activating partner (usually another protein domain), which is accompanied by insertion of stimulatory moieties (usually arginine or lysine residues) into the catalytic sites. After inspecting over 3600 Mg-NTP-containing structures of P-loop NTPases, we identified those with stimulator(s) inserted into catalytic sites and analysed the patterns of stimulatory interactions. In most cases, at least one stimulator twists gamma-phosphate counter-clockwise by linking the oxygen atoms of alpha- and gamma-phosphates; the twisted gamma-phosphate is stabilized by a hydrogen bond with the backbone amino group of the fourth residue of the Walker A motif. In the remaining cases, the stimulators only interact with gamma-phosphate. The all-pervasive mechanistic interactions of diverse stimulators with the gamma phosphate group suggests its twisting/turning as the trigger for NTP hydrolysis.

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A Distinct Motif in a Prokaryotic Small Ras-Like GTPase Highlights Unifying Features of Walker B Motifs in P-Loop NTPases

Cited by 15 publications

References 49 publications

Common mechanism of activated catalysis in P-loop fold nucleoside triphosphatases -in varietate concordia

Common mechanism of activated catalysis in P-loop fold nucleoside triphosphatases -in varietate concordia

On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment

Common patterns of hydrolysis initiation in P-loop fold nucleoside triphosphatases

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