Two ATPases

Senior, Alan E.

doi:10.1074/jbc.x112.402313

Cited by 22 publications

(14 citation statements)

References 87 publications

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“…Despite the high ATP concentration in the crystallization solution (5 mM), ATPase 1 contains a sulfate ion in the active site (Figure 3A) whereas ATPase 2 and ATPase 3 are bound to ATP as they were in the signal sequence-bound structure (Figure 2). Several structural features of the ATPase 1 catalytic site are strongly reminiscent of the ATP “empty” (β E ) subunit of the F 1 -ATPase (Figure 3D and 3E) which is known to have a very low affinity for nucleotide (Menz et al, 2001; Senior, 2012). In particular, the Walker A lysine is rotated into an unfavorable rotamer and bound to the Walker B aspartate, displacing the binding of magnesium in the active site and likely preventing binding of ATP.…”

Section: Resultsmentioning

confidence: 99%

Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion

Rosenberg

Dovala

et al. 2015

Cell

133

200

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Summary Mycobacterium tuberculosis and Staphylococcus aureus secrete virulence factors via Type VII protein secretion (T7S), a system that intriguingly requires all of its secretion substrates for activity. To gain insights into T7S function, we used structural approaches to guide studies of the putative translocase EccC, a unique enzyme with three ATPase domains, and its secretion substrate EsxB. The crystal structure of EccC revealed that the ATPase domains are joined by linker/pocket interactions that modulate its enzymatic activity. EsxB binds via its signal sequence to an empty pocket on the C-terminal ATPase domain, which is accompanied by an increase in ATPase activity. Surprisingly, substrate binding does not activate EccC allosterically, but rather by stimulating its multimerization. Thus, the EsxB substrate is also an integral T7S component, illuminating a mechanism that helps explain interdependence of substrates and suggests a model in which binding of substrates modulates their coordinate release from the bacterium.

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Section: Resultsmentioning

confidence: 99%

Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion

Rosenberg

Dovala

et al. 2015

Cell

133

200

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“…For example, the efflux transporter P-glycoprotein (ABCB1) [34] exports an enormous range of structurally distinct xenobiotics, at the expense of very specific ATP hydrolysis. Arguably, the enzyme is substrate promiscuous with respect to export but not catalytically promiscuous with respect to ATP hydrolysis, even though many different transported substrates activate the hydrolysis.…”

Section: Definitionsmentioning

confidence: 99%

Biological messiness vs. biological genius: Mechanistic aspects and roles of protein promiscuity

Atkins

2015

The Journal of Steroid Biochemistry and Molecular Biology

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In contrast to the traditional biological paradigms focused on ‘specificity’, recent research and theoretical efforts have focused on functional ‘promiscuity’ exhibited by proteins and enzymes in many biological settings, including enzymatic detoxication, steroid biochemistry, signal transduction and immune responses. In addition, divergent evolutionary processes are apparently facilitated by random mutations that yield promiscuous enzyme intermediates. The intermediates, in turn, provide opportunities for further evolution to optimize new functions from existing protein scaffolds. In some cases, promiscuity may simply represent the inherent plasticity of proteins resulting from their polymeric nature with distributed conformational ensembles. Enzymes or proteins that bind or metabolize noncognate substrates create ‘messiness’ or noise in the systems they contribute to. With our increasing awareness of the frequency of these promiscuous behaviors it becomes interesting and important to understand the molecular bases for promiscuous behavior and to distinguish between evolutionarily selected promiscuity and evolutionarily tolerated messiness. This review provides an overview of current understanding of these aspects of protein biochemistry and enzymology.

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“…The central role of ATP synthase as a biological nanomotor to generate or hydrolyze ATP, the universal energy currency is well established [1–3]. Lately, the presence of ATP synthase on the cell surface and its involvement in multiple cell functions has become known.…”

Section: Introductionmentioning

confidence: 99%

Asp residues of βDELSEED-motif are required for peptide binding in the Escherichia coli ATP synthase

Ahmad

Tayou

Laughlin

2015

International Journal of Biological Macromolecules

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This study demonstrates the requirement of Asp-380 and Asp-386 in the βDELSEED-motif of E. coli ATP synthase for peptide binding and inhibition. We studied the inhibition profiles of wild-type and mutant E. coli ATP synthase in presence of c-terminal amide bound melittin and melittin related peptide. Melittin and melittin related peptide inhibited wild-type ATPase almost completely while only partial inhibition was observed in single mutations with replacement of Asp to Ala, Gln, or Arg. Additionally, very little or no inhibition occurred among double mutants βD380A/βD386A, βD380Q/βD386Q, or βD380R/βD386R signifying that removal of one Asp residue allows limited peptide binding. Partial or substantial loss of oxidative phosphorylation among double mutants demonstrates the functional requirement of βD380 and βD386 Asp residues. Moreover, abrogation of wild-type E. coli cell growth and normal growth of mutant cells in presence of peptides provides strong evidence for the requirement of βDELSEED-motif Asp residues for peptide binding. It is concluded that while presence of one Asp residue may allow partial peptide binding, both Asp residues, βD380 and βD386, are essential for proper peptide binding and inhibition of ATP synthase.

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Two ATPases

Cited by 22 publications

References 87 publications

Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion

Substrates Control Multimerization and Activation of the Multi-Domain ATPase Motor of Type VII Secretion

Biological messiness vs. biological genius: Mechanistic aspects and roles of protein promiscuity

Asp residues of βDELSEED-motif are required for peptide binding in the Escherichia coli ATP synthase

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