Lessons From Zinc-Binding Peptides

Berg, Jeremy M.; Godwin, Hilary

doi:10.1146/annurev.biophys.26.1.357

Cited by 243 publications

(282 citation statements)

References 46 publications

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“…Metals perform a variety of tasks in cells from structural stabilization to enzyme catalysis, activating key life processes such as respiration and photosynthesis [36,37]. The Na, K, Mg, Ca, Zn, Cu, Fe, Co and Mn are the most frequently observed in proteins under physiological conditions; and among those, Zn plays essential roles as cofactor of metabolic enzymes and transcription factors.…”

Section: Zinc Ions Stabilise the Tetrameric Structure Of Smeldhpmentioning

confidence: 99%

Metal-triggered changes in the stability and secondary structure of a tetrameric dihydropyrimidinase: A biophysical characterization

Martínez‐Rodríguez

Encinar

Hurtado-Gómez

et al. 2009

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 3 ABSTRACTDihydropyrimidinase is involved in the reductive pathway of pyrimidine degradation, catalysing the reversible hydrolysis of the cyclic amide bond (-CO-NH-) of 5,6-dihydrouracil and 5,6-dihydrothymine to the corresponding N-carbamoyl-β-amino acids. This enzyme is an attractive candidate for commercial production of D-amino acids, which are used in the production of semisynthetic β-lactams, antiviral agents, artificial sweeteners, peptide hormones and pesticides. We have obtained the crystal structure of the dihydropyrimidinase from Sinorhizobium meliloti (SmelDhp) in the presence of zinc ions, but we have not been able to obtain good diffracting crystals in its absence. Then, the role of the ion in the structure of the protein, and in its stability, remains to be elucidated. In this work, the stability and the structure of SmelDhp have been studied in the absence and in the presence of zinc. In its absence, the protein acquired a tetrameric functional structure at pH ~6.0, which is stable up to pH ~9.0, as concluded from fluorescence and CD.Chemical-denaturation occurred via a monomeric intermediate with non-native structure. The addition of zinc caused: (i) an increase of the helical structure, and changes in the environment of aromatic residues; and, (ii) a higher thermal stability. However, chemical-denaturation still occurred through a monomeric intermediate. This is the first hydantoinase whose changes in the stability and in the secondary structure upon addition of zinc are described and explained, and one of the few examples where the zinc exclusively alters the secondary helical structure and the environment of some aromatic residues in the protein, leaving unchanged the quaternary structure.

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Section: Zinc Ions Stabilise the Tetrameric Structure Of Smeldhpmentioning

confidence: 99%

Metal-triggered changes in the stability and secondary structure of a tetrameric dihydropyrimidinase: A biophysical characterization

Martínez‐Rodríguez

Encinar

Hurtado-Gómez

et al. 2009

Biophysical Chemistry

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“…Zinc fingers often bind other divalent cations (32). To gain insight into whether Zn 2ϩ is the physiological ligand of Mcm10, NMR spectra of the ZFMcm10Ј peptide were collected in the presence of several other divalent cations.…”

Section: Zn 2ϩ Binding-dependent Mcm10 Homocomplex Formation 36054mentioning

confidence: 99%

“…Several classes of zinc fingers such as the CCHH, CCCC, CCHC, and CHCC families, categorized based on arrangements of the conserved cysteines and/or histidines in the motifs, have been characterized and shown to modulate their host proteins' interactions with DNA, RNA, or other proteins (32,33). CCCH-type zinc fingers were recently identified in a number of RNA-binding proteins (31,34) and shown to regulate degradation of retroviral (35) and tumor necrosis factor mRNAs in mammalian cells (31).…”

mentioning

confidence: 99%

A Novel Zinc Finger Is Required for Mcm10 Homocomplex Assembly

Cook

Kung

Peterson

et al. 2003

Journal of Biological Chemistry

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Mcm10 is a DNA replication factor that interacts with multiple subunits of the MCM2-7 hexameric complex. We report here that Mcm10 self-interacts and assembles into large homocomplexes (ϳ800 kDa). A conserved domain of 210 amino acid residues is sufficient for mediating self-interaction and complex assembly. A novel zinc finger within the conserved domain, CX 10 CX 11 CX 2 H, is essential for the homocomplex formation. Mutant alleles with amino acid substitutions at conserved cysteines and histidine in the zinc finger fail to assemble homocomplexes. A defect in homocomplex assembly correlates with defects in DNA replication and cell growth in the mutants. These observations suggest that homocomplex assembly is essential for Mcm10 function. Multisubunit Mcm10 homocomplexes may provide the structural basis for Mcm10 to interact with multiple subunits of the MCM2-7 hexamer.

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“…It is even unclear whether the Zn(II) binds to the peptide at early stage of folding and induces the peptide folding, or the Zn(II) just binds to the peptide at the end of folding and stabilizes the native structure 26,27 .…”

Section: Introductionmentioning

confidence: 99%

Metal-Coupled Folding of Cys₂His₂ Zinc-Finger

et al. 2007

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Zinc-fingers, which widely exist in eukaryotic cell and play crucial roles in life processes, depend on the binding of zinc ion for their proper folding. To computationally study the zinc coupled folding of the zinc-fingers, charge transfer and metal induced protonation/deprotonation effects have to be considered. Here, by attempting to implicitly account for such effects in classical molecular dynamics and performing intensive simulations with explicit solvent for the peptides with and without zinc binding, we investigate the folding of the Cys 2 His 2 type zinc-finger motif and the coupling between the peptide folding and zinc binding. We find that zinc ion not only stabilizes the native structure, but also participates in the whole folding process. It binds to the peptide at early stage of folding, and directs or modulates the folding and stabilizations of the component β-hairpin and α-helix. Such a crucial role of zinc binding is mediated by the packing of the conserved hydrophobic residues. We also find that the packing of the hydrophobic residues and the coordination of the native ligands are coupled. Meanwhile, the processes of zinc binding, mis-ligation, ligand exchange and zinc induced secondary structure conversion, as well as the water behaviour, due to the involvement of zinc ion are characterized. Our results are in good agreement with related experimental observations, and provide significant insight into the general mechanisms of the metal-cofactor dependent protein folding and other metal induced conformational changes of biological importance.

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Lessons From Zinc-Binding Peptides

Cited by 243 publications

References 46 publications

Metal-triggered changes in the stability and secondary structure of a tetrameric dihydropyrimidinase: A biophysical characterization

Metal-triggered changes in the stability and secondary structure of a tetrameric dihydropyrimidinase: A biophysical characterization

A Novel Zinc Finger Is Required for Mcm10 Homocomplex Assembly

Metal-Coupled Folding of Cys₂His₂ Zinc-Finger

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Lessons From Zinc-Binding Peptides

Cited by 243 publications

References 46 publications

Metal-triggered changes in the stability and secondary structure of a tetrameric dihydropyrimidinase: A biophysical characterization

Metal-triggered changes in the stability and secondary structure of a tetrameric dihydropyrimidinase: A biophysical characterization

A Novel Zinc Finger Is Required for Mcm10 Homocomplex Assembly

Metal-Coupled Folding of Cys2His2 Zinc-Finger

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Metal-Coupled Folding of Cys₂His₂ Zinc-Finger