Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Apr 23;114(8):4206-28.
doi: 10.1021/cr4004488. Epub 2013 Dec 26.

Nonredox nickel enzymes

Michael J Maroney  1 , Stefano Ciurli
Affiliations
Review

Nonredox nickel enzymes

Michael J Maroney et al. Chem Rev. .

Abstract

PubMed Disclaimer

Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Ribbon scheme of the functional oligomer (αβγ)3 of B. pasteurii urease. (B) Ribbon scheme of the functional oligomer (αβγ)3 of K. aerogenes urease. (C) Ribbon scheme of the functional oligomer [(αβ)3]4 of H. pylori urease seen through the ternary axis (left panel) and rotated by 90° along the horizontal axis (right panel). (D) Ribbon scheme of the functional oligomer [(α)3]2 of C. ensiformis urease seen through the ternary axis (left panel) and rotated by 90° along the horizontal axis (right panel).
Figure 2
Figure 2
Ribbon scheme of the active site flap of B. pasteurii urease, highlighting the open and closed conformations observed in the native and the DAP-inhibited structures, respectively.
Figure 3
Figure 3
CrystalMaker drawing of the crystallographic structural models for the active site obtained for B. pasteurii urease (PDB code 2UBP) in the native state. The nickel ions are represented in gray, while CPK coloring is used for all other atoms. Hydrogen bonds are shown as thin blue lines. The BPU residue-numbering scheme (all residues belonging to the α subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 4
Figure 4
CrystalMaker drawing of the crystallographic structural model for the active site obtained for B. pasteurii urease complexed with β-mercaptoethanol (BME) (PDB code 1UBP). The nickel ions are represented in gray, while CPK coloring is used for all other atoms. Hydrogen bonds are shown as thin blue lines. The BPU residue-numbering scheme (all residues belonging to the α subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 5
Figure 5
CrystalMaker drawing of the crystallographic structural model for the active site obtained for urease from B. pasteurii complexed with acetohydroxamic acid (AHA) (PDB code 4UBP). The nickel ions are represented in gray, while CPK coloring is used for all other atoms. Hydrogen bonds are shown as thin blue lines. The BPU residue-numbering scheme (all residues belonging to the α subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 6
Figure 6
CrystalMaker drawing of the crystallographic structural model for the active site obtained for B. pasteurii urease complexed with phosphate (PHO) (PDB code 1IE7). The nickel ions are represented in gray and phosphorus is in orange, while CPK coloring is used for all other atoms. WAT = solvent molecule. Hydrogen bonds are shown as thin blue lines. The BPU residue-numbering scheme (all residues belonging to the α subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 7
Figure 7
CrystalMaker drawing of the crystallographic structural model for the active site obtained for B. pasteurii urease complexed with boric acid B(OH)3 (PDB code 1S3T). The nickel ions are represented in gray and boron is in green, while CPK coloring is used for all other atoms. WB = nickel-bridging hydroxide. Hydrogen bonds are shown as thin blue lines. The BPU residue-numbering scheme (all residues belonging to the α subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 8
Figure 8
CrystalMaker drawing of the crystallographic structural model for the active site obtained for B. pasteurii urease complexed with diaminophosphate (DAP) (PDB code 3UBP). The nickel ions are represented in gray and phosphorus is in orange, while CPK coloring is used for all other atoms. Hydrogen bonds are shown as thin blue lines. The BPU residue-numbering scheme (all residues belonging to the α subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 9
Figure 9
CrystalMaker drawing of the crystallograhic structural model for the active site obtained for B. pasteurii urease complexed with citrate (PDB code 4AC7). The nickel ions are represented in gray, while CPK coloring is used for all other atoms. The BPU residue-numbering scheme (all residues belonging to the alpha subunit) is used. The residue indicated with the letter “K” is the carbamylated lysine.
Figure 10
Figure 10
Structure-based urease catalytic mechanism of the enzymatic hydrolysis of urea. The BPU residue-numbering scheme is used.
Figure 11
Figure 11
Sequence alignments of selected class I and class II glyoxalase I enzymes created using Clustal W2. Amino acids are colored by property (hydrophobic (red), acidic (blue), basic (purple), other (green)). Metal binding residues are highlighted in yellow. Residues marked with an asterisk (∗) are invariant; those marked by other symbols represent low (:) and moderate (.) variability. The N-terminal extension and additional loops found in class I enzymes are highlighted in blue. The S. cerevisiae sequence was truncated after 226 of 326 residues.
Figure 12
Figure 12
Ribbon diagram of the crystal structure of E. coli Glo I, (PDB code 1F9Z) showing the two subunits of the homo dimer in cyan and gray and the location of the two Ni sites (green spheres) at subunit interfaces.
Figure 13
Figure 13
Comparison of the metal site structure of the Ni(II) complex (panel A, PDB code 1F9Z) and the Zn(II) complex (panel B, 1FA5) of E. coli Glo I showing the change in coordination number and geometry for the two metals. The nickel and zinc ions are represented in gray and dark blue, respectively, while CPK coloring is used for all other atoms. WAT = solvent molecules. Protein residues are distinguished by letters indicating the two different subunits of the enzyme.
Figure 14
Figure 14
Putative reaction mechanism for the isomerization catalyzed by Glo I that involves coordination of the substrate.
Figure 15
Figure 15
Simplified diagram of the methionine salvage pathway, illustrating key products, intermediates, and catalysis by Ni-ARD vs Fe-ARD.
Figure 16
Figure 16
Sequence alignments of selected ARD enzymes created using Clustal W2. The sequences are numbered from Met0, since this residue is cleaved in the mature enzyme. Amino acids are colored by property (hydrophobic (red), acidic (blue), basic (purple), other (green)). Metal binding residues are highlighted in yellow. Residues marked with an asterisk (∗) are invariant; those marked by other symbols represent low (:) and moderate (.) variability.
Figure 17
Figure 17
Ribbon diagram of the NMR structure of K. oxytoca Ni-ARD (PDB code 1ZRR) showing the cupin fold and the location of the metal ion (green sphere) with the ligand environment shown as sticks.
Figure 18
Figure 18
Metal site structure of K. oxytoca Ni-ARD (PDB code 1ZRR), showing the His3Glu coordination of the metal site and the two cis-aqua ligands in the positions used in binding substrate. The nickel ion is represented in gray, while CPK coloring is used for all other atoms. WAT = solvent molecules.
Figure 19
Figure 19
Proposed reaction mechanism illustrating the chelate hypothesis to explain the regioselectivity of the reactions catalyzed by Ni-ARD vs Fe-ARD. The results of incorporation of 18O and 14C labeling studies are indicated by the red O atoms and the asterisks (∗). (Adapted with permission from ref . Copyright 2007 John Wiley & Sons, Ltd.)
Figure 20
Figure 20
Model chemistry illustrating the role of substrate hydration in determining the regioselectivity of the reactions catalyzed by Ni-ARD vs Fe-ARD.
Figure 21
Figure 21
Mechanisms for Ni-ARD vs Fe-ARD catalysis from computational modeling indicate that the electronic structure of the metal ions leads to additional intermediates in the Fe-ARD reaction pathway.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
See this image and copyright information in PMC

References

    1. Sigel A, Sigel H, Sigel RKO, editors. Nickel and Its Surprising Impact on Nature. John Wiley & Sons, Ltd.; Chichester, England: 2007.
    1. Zambelli B, Ciurli S. Nickel and human health. In: Sigel A, Sigel H, Sigel RKO, editors. Interrelations between Essential Metal Ions and Human Diseases. Vol. 13 Springer Science and Business Media B.V.; Dordrecht, Germany: 2014.
    1. Chen H, Giri NC, Zhang R, Yamane K, Zhang Y, Maroney M, Costa M. J Biol Chem. 2010;285:7374. - PMC - PubMed
    1. Giri NC, Passantino L, Sun H, Zoroddu MA, Costa M, Maroney MJ. Biochemistry. 2013;52:4168. - PMC - PubMed
    2. Giri NC, Sun H, Chen H, Costa M, Maroney MJ. Biochemistry. 2011;50:5067. - PMC - PubMed
    1. Torres F, das Gracas M, Melo M, Tosti A. Clin, Cosmet Invest Dermatol. 2009;2:39. - PMC - PubMed

LinkOut - more resources