ArticleBiochemistry2015
Mutational and Computational Evidence That a Nickel-Transfer Tunnel in UreD Is Used for Activation of Klebsiella aerogenes Urease.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 46 citations in OpenAlex.
- Elp3 uses a conserved molecular tunnel to transport acetate between distant active sites and catalyze tRNA wobble base modification.Nature communications · 2026Article
- Structural landscape of bacterial urease: implications for catalyst and adaptation.Archives of microbiology · 2026Review
- Moving metals: How microbes deliver metal cofactors to metalloproteins.Molecular microbiology · 2023Article
- Delivering a toxic metal to the active site of urease.Science advances · 2023Article
- Structural characterization of the urease accessory protein UreF from Klebsiella pneumoniae.Acta crystallographica. Section F, Structural biology communications · 2022Article
- COG0523 proteins: a functionally diverse family of transition metal-regulated G3E P-loop GTP hydrolases from bacteria to man.Metallomics : integrated biometal science · 2021Article
- Targeting the Protein Tunnels of the Urease Accessory Complex: A Theoretical Investigation.Molecules (Basel, Switzerland) · 2020Article
- Structure, function, and biosynthesis of nickel-dependent enzymes.Protein science : a publication of the Protein Society · 2020Review
- Genomics of Urea Transport and Catabolism in Cyanobacteria: Biotechnological Implications.Frontiers in microbiology · 2019Review
- Ureases: Historical aspects, catalytic, and non-catalytic properties - A review.Journal of advanced research · 2018Review
- A Structural Model of the Urease Activation Complex Derived from Ion Mobility-Mass Spectrometry and Integrative Modeling.Structure (London, England : 1993) · 2018Article
- Structural insights into how GTP-dependent conformational changes in a metallochaperone UreG facilitate urease maturation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The assembly of the plant urease activation complex and the essential role of the urease accessory protein G (UreG) in delivery of nickel to urease.The Journal of biological chemistry · 2017Article
- A Bacillus paralicheniformis Iron-Containing Urease Reduces Urea Concentrations in Rice Wine.Applied and environmental microbiology · 2017Article
- Non-thiolate ligation of nickel by nucleotide-free UreG of Klebsiella aerogenes.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
- Sumner's legacy: a century of urease crystals and recent structural advances.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nickel-containing urease from Klebsiella aerogenes requires four accessory proteins for proper active site metalation. The metallochaperone UreE delivers nickel to UreG, a GTPase that forms a UreD/UreF/UreG complex, which binds to urease apoprotein via UreD. Prior in silico analysis of the homologous, structurally characterized UreH/UreF/UreG complex from Helicobacter pylori identified a water tunnel originating at a likely nickel-binding motif in UreG, passing through UreF, and exiting UreH, suggestive of a role for the channel in providing the metal to urease apoprotein for its activation; however, no experimental support was reported for the significance of this tunnel. Here, specific variants were designed to disrupt a comparable 34.6 Å predicted internal tunnel, alternative channels, and surface sites for UreD. Cells producing a set of tunnel-disrupting variants of UreD exhibited greatly reduced urease specific activities, whereas other mutants had no appreciable effect on activity. Affinity pull-down studies of cell-free extracts from tunnel-disrupting mutant cultures showed no loss of UreD interactions with urease or UreF/UreG. The nickel contents of urease samples enriched from activity-deficient cultures were decreased, while zinc and iron incorporation increased. Molecular dynamics simulations revealed size restrictions in the internal channels of the UreD variants. These findings support the role of a molecular tunnel in UreD as a direct facilitator of nickel transfer into urease, illustrating a new paradigm in active site metallocenter assembly.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.