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Nickel management by the accessory protein UreG during urease activation.

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Τίτλος: Nickel management by the accessory protein UreG during urease activation.
Συγγραφείς: Frumenzio G; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Piero Gobetti 87, 40129, Bologna, Italy; Super Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033, Casalecchio di Reno, Italy., Emerson A; Super Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033, Casalecchio di Reno, Italy., Ciurli S; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Piero Gobetti 87, 40129, Bologna, Italy., Musiani F; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Piero Gobetti 87, 40129, Bologna, Italy. Electronic address: francesco.musiani@unibo.it.
Πηγή: International journal of biological macromolecules [Int J Biol Macromol] 2026 Sep; Vol. 374, pp. 153277. Date of Electronic Publication: 2026 Jun 30.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier
Original Publication: Guildford, Eng., IPC Science and Technology Press.
Ιατρικοί όροι (MeSH): Nickel*/metabolism , Nickel*/chemistry , Urease*/metabolism , Urease*/chemistry , Bacterial Proteins*/chemistry , Bacterial Proteins*/metabolism, Guanosine Triphosphate/metabolism ; Molecular Dynamics Simulation ; Hydrolysis ; Enzyme Activation ; Binding Sites ; Protein Binding ; Hydrogen Bonding ; Phosphate-Binding Proteins
Περίληψη: Urease is a nickel-dependent metalloenzyme whose activation requires the coordinated action of four accessory proteins that mediate Ni(II) trafficking and insertion into the active site. Among these proteins, UreG is the first reported case of an intrinsically disordered GTPase that transiently binds Ni(II) through a conserved Cys-Pro-His (CPH) motif and is thought to regulate metal delivery during urease maturation. In this study, we investigated how GTP hydrolysis affects Ni(II) binding and the structural dynamics of Klebsiella pneumoniae UreG using extended all-atom molecular dynamics simulations in explicit solvent. Removal of the GTP γ-phosphate group and Mg(II) ion, thus modeling the effects of GTP hydrolysis, destabilizes the hydrogen-bonding network that connects the nucleotide-binding pocket to the CPH motif. This disruption increases the tendency of the UreG homodimer to undergo structural rearrangement, enhancing its flexibility, as well as displacing the Ni(II)-binding region outward, rendering it more exposed to the aqueous environment. Nevertheless, Ni(II) remains coordinated to the CPH motif throughout all simulations. These results support a model in which GTP hydrolysis primes UreG for Ni(II) transfer by weakening the structural constraints around the metal-binding site, rather than directly triggering metal release. Additional interactions, likely involving the accessory protein UreF, are required to promote nickel release and complete urease activation.
(Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: GTP hydrolysis; Metallochaperone; Molecular dynamics; Nickel trafficking; UreG; Urease activation
Substance Nomenclature: 7OV03QG267 (Nickel)
EC 3.5.1.5 (Urease)
0 (ureG protein, Bacteria)
0 (Bacterial Proteins)
86-01-1 (Guanosine Triphosphate)
0 (Phosphate-Binding Proteins)
Entry Date(s): Date Created: 20260630 Date Completed: 20260821 Latest Revision: 20260821
Update Code: 20260821
DOI: 10.1016/j.ijbiomac.2026.153277
PMID: 42379439
Βάση Δεδομένων: MEDLINE
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  Data: Nickel management by the accessory protein UreG during urease activation.
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  Data: <searchLink fieldCode="AU" term="%22Frumenzio+G%22">Frumenzio G</searchLink>; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Piero Gobetti 87, 40129, Bologna, Italy; Super Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033, Casalecchio di Reno, Italy.<br /><searchLink fieldCode="AU" term="%22Emerson+A%22">Emerson A</searchLink>; Super Computing Applications and Innovation, Department HPC, CINECA, via Magnanelli 6/3, 40033, Casalecchio di Reno, Italy.<br /><searchLink fieldCode="AU" term="%22Ciurli+S%22">Ciurli S</searchLink>; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Piero Gobetti 87, 40129, Bologna, Italy.<br /><searchLink fieldCode="AU" term="%22Musiani+F%22">Musiani F</searchLink>; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Piero Gobetti 87, 40129, Bologna, Italy. Electronic address: francesco.musiani@unibo.it.
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  Data: <searchLink fieldCode="JN" term="%227909578%22">International journal of biological macromolecules</searchLink> [Int J Biol Macromol] 2026 Sep; Vol. 374, pp. 153277. <i>Date of Electronic Publication: </i>2026 Jun 30.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier%22">Elsevier </searchLink><i>Country of Publication: </i>Netherlands <i>NLM ID: </i>7909578 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1879-0003 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2201418130%22">01418130 </searchLink><i>NLM ISO Abbreviation: </i>Int J Biol Macromol <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: Amsterdam : Elsevier<br /><i>Original Publication</i>: Guildford, Eng., IPC Science and Technology Press.
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  Data: <searchLink fieldCode="MM" term="%22Nickel%22">Nickel*</searchLink>/<searchLink fieldCode="MM" term="%22Nickel+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Nickel%22">Nickel*</searchLink>/<searchLink fieldCode="MM" term="%22Nickel+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+metabolism%22">metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Guanosine+Triphosphate%22">Guanosine Triphosphate</searchLink>/<searchLink fieldCode="MH" term="%22Guanosine+Triphosphate+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Molecular+Dynamics+Simulation%22">Molecular Dynamics Simulation</searchLink> ; <searchLink fieldCode="MH" term="%22Hydrolysis%22">Hydrolysis</searchLink> ; <searchLink fieldCode="MH" term="%22Enzyme+Activation%22">Enzyme Activation</searchLink> ; <searchLink fieldCode="MH" term="%22Binding+Sites%22">Binding Sites</searchLink> ; <searchLink fieldCode="MH" term="%22Protein+Binding%22">Protein Binding</searchLink> ; <searchLink fieldCode="MH" term="%22Hydrogen+Bonding%22">Hydrogen Bonding</searchLink> ; <searchLink fieldCode="MH" term="%22Phosphate-Binding+Proteins%22">Phosphate-Binding Proteins</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Urease is a nickel-dependent metalloenzyme whose activation requires the coordinated action of four accessory proteins that mediate Ni(II) trafficking and insertion into the active site. Among these proteins, UreG is the first reported case of an intrinsically disordered GTPase that transiently binds Ni(II) through a conserved Cys-Pro-His (CPH) motif and is thought to regulate metal delivery during urease maturation. In this study, we investigated how GTP hydrolysis affects Ni(II) binding and the structural dynamics of Klebsiella pneumoniae UreG using extended all-atom molecular dynamics simulations in explicit solvent. Removal of the GTP γ-phosphate group and Mg(II) ion, thus modeling the effects of GTP hydrolysis, destabilizes the hydrogen-bonding network that connects the nucleotide-binding pocket to the CPH motif. This disruption increases the tendency of the UreG homodimer to undergo structural rearrangement, enhancing its flexibility, as well as displacing the Ni(II)-binding region outward, rendering it more exposed to the aqueous environment. Nevertheless, Ni(II) remains coordinated to the CPH motif throughout all simulations. These results support a model in which GTP hydrolysis primes UreG for Ni(II) transfer by weakening the structural constraints around the metal-binding site, rather than directly triggering metal release. Additional interactions, likely involving the accessory protein UreF, are required to promote nickel release and complete urease activation.<br /> (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>GTP hydrolysis; Metallochaperone; Molecular dynamics; Nickel trafficking; UreG; Urease activation
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 7OV03QG267 (Nickel)<br />EC 3.5.1.5 (Urease)<br />0 (ureG protein, Bacteria)<br />0 (Bacterial Proteins)<br />86-01-1 (Guanosine Triphosphate)<br />0 (Phosphate-Binding Proteins)
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  Data: <i>Date Created: </i>20260630 <i>Date Completed: </i>20260821 <i>Latest Revision: </i>20260821
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  Data: 10.1016/j.ijbiomac.2026.153277
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  Data: 42379439
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42379439
RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.ijbiomac.2026.153277
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 153277
    Subjects:
      – SubjectFull: Guanosine Triphosphate metabolism
        Type: general
      – SubjectFull: Molecular Dynamics Simulation
        Type: general
      – SubjectFull: Hydrolysis
        Type: general
      – SubjectFull: Enzyme Activation
        Type: general
      – SubjectFull: Binding Sites
        Type: general
      – SubjectFull: Protein Binding
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      – SubjectFull: Hydrogen Bonding
        Type: general
      – SubjectFull: Phosphate-Binding Proteins
        Type: general
      – SubjectFull: Nickel metabolism
        Type: general
      – SubjectFull: Nickel chemistry
        Type: general
      – SubjectFull: Urease metabolism
        Type: general
      – SubjectFull: Urease chemistry
        Type: general
      – SubjectFull: Bacterial Proteins chemistry
        Type: general
      – SubjectFull: Bacterial Proteins metabolism
        Type: general
    Titles:
      – TitleFull: Nickel management by the accessory protein UreG during urease activation.
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              Text: 2026 Sep
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