New model potentials for sulfur–copper(I) and sulfur–mercury(II) interactions in proteins: From <i>ab initio</i> to molecular dynamics

Fuchs, Jean-François; Nedev, Hristo; Poger, David; Ferrand, Michel; Brenner, V.; Dognon, Jean-Pierre; Crouzy, Serge

doi:10.1002/jcc.20392

Cited by 22 publications

(27 citation statements)

References 62 publications

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“…The endoglucanase inhibition by the Hg ion has been shown in different studies [Ferchak and Pye, 1983;Mandels and Reese, 1965], which is supported by a Cys mutation study [Ai et al, 2003]. The thiol groups can capture mercury, and thiolates (R-S-) and thioketones (R2-C = S) form a strong complex with Hg ions [Fuchs et al, 2006;Manceau and Nagy, 2008]. The present 3D structure and catalytic insights to the ST15c10 endoglucanase support our biochemical experimentation related to enzymatic regulations.…”

Section: Discussionsupporting

confidence: 60%

The Dual Carboxymethyl Cellulase and Gelatinase Activities of a Newly Isolated Protein from Brevibacillus agri ST15c10 Confer Reciprocal Regulations in Substrate Utilization

Maiti

Samanta²,

Sahoo³

et al. 2017

Microb Physiol

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A protein showing endoglucanase-peptidase activity was prepared from a newly isolated bacterium (ST15c10). We identified ST15c10 as Brevibacillus agri based on electron-microscopic images and its 16S-rDNA sequence (GenBank accession No. HM446043), which exhibits 98.9% sequence identity to B. agri (KZ17)/B. formosus (DSM-9885T)/B. brevis. The enzyme was purified to homogeneity and gave a single peak during high-performance liquid chromatography on a Seralose 6B-150 gel-matrix/C-18 column. MALDI-TOF mass-spectrometry and bioinformatics studies revealed significant similarity to M42-aminopeptidases/endoglucanases of the CelM family. These enzymes are found in all Brevibacillus strains for which the genome sequence is known. ST15c10 grows optimally on carboxymethyl cellulose (CMC)-gelatin (40°C/pH 8-9), and also shows strong growth/carboxymethyl cellulase (CMCase) activity in submerged bagasse fermentation. The purified enzyme also functions as endoglucanase with solid bagasse/rice straw. Its CMCase activity (optimal at pH 5.6 and 60°C/K_m = 35.5 µM/V_max = 1,024U) was visualized by zymography on a CMC-polyacrylamide gel, which provided a strong band of approximately 70 kDa. The purified enzyme also showed strong peptidase (gelatinase) activity (pH 7.2/40°C during zymography on 6-12% gelatin/1% gelatin-PAGE (at approx. 70 kDa). The CMCase activity is inhibited by the metal ions Mn/Cu/Fe/Co (50%), Hg/KMnO₄ (100%), and by glucose or lactose (50-75%; all at 1 mM). The observed dose/time-dependent inhibition by Hg ions could be prevented with 2-mercaptoethanol. A comparison of the B. agri endoglucanase-aminopeptidase (ELK43520; 350 aa) with other members of the M42-family revealed the conservation of active-site residues Cys256/Cys260, which were previously identified as metal-binding sites. Regulation of the endoglucanase activity probably occurs via metal binding-triggered changes in the redox state of the enzyme. Studies on this type of enzyme are of high importance for basic scientific and industrial research.

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Section: Discussionsupporting

confidence: 60%

The Dual Carboxymethyl Cellulase and Gelatinase Activities of a Newly Isolated Protein from Brevibacillus agri ST15c10 Confer Reciprocal Regulations in Substrate Utilization

Maiti

Samanta²,

Sahoo³

et al. 2017

Microb Physiol

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“…Two MD simulations of free-IDE and IDE-Cu + were run, by using the NAMD code, [48] with the amber99SB force field and TIP3P model for water. [49] Cu + -sulfur potential [50] was used to treat the binding of Cu + to cysteines 812 and 819. To assess the trustworthiness of the Cu + -sulfur potential in combination with Amber99SB force field, an additional control simulation was carried out on the structure of ATX1, the yeast Cu I metallochaperone.…”

mentioning

confidence: 99%

Copper(I) and Copper(II) Inhibit Aβ Peptides Proteolysis by Insulin‐Degrading Enzyme Differently: Implications for Metallostasis Alteration in Alzheimer’s Disease

Grasso

Pietropaolo

Spoto

et al. 2011

Chemistry A European J

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Accumulation of neurotoxic amyloid-β peptide (Aβ) and alteration of metal homeostasis (metallostasis) in the brain are two main factors that have been very often associated with neurodegenerative diseases, such as Alzheimer's disease (AD). Aβ is constantly produced from the amyloidprecursor-protein APP precursor and immediately catabolized under normal conditions, whereas dysmetabolism of Aβ and/or metal ions seems to lead to a pathological deposition. Although insulin-degrading enzyme (IDE) is the main metalloprotease involved in Aβ degradation in the brain being up-regulated in some areas of AD brains, the role of IDE for the onset and development of AD is far from being understood. Moreover, the biomolecular mechanisms involved in the recognition and interaction between IDE and its substrates are still obscure. In spite of the important role of metals (such as copper, aluminum, and zinc), which has brought us to propose a "metal hypothesis of AD", a targeted study of the effect of metallostasis on IDE activity has never been carried out. In this work, we have investigated the role that various metal ions (i.e., Cu(2+), Cu(+), Zn(2+), Ag(+), and Al(3+)) play in modulating the interaction between IDE and two Aβ peptide fragments, namely Aβ(1-16) and Aβ(16-28). It was therefore possible to identify the direct effect that such metal ions have on IDE structure and enzymatic activity without interferences caused by metal-induced substrate modifications. Mass spectrometry and kinetic studies revealed that, among all the metal ions tested, only Cu(2+), Cu(+), and Ag(+) have an inhibitory effect on IDE activity. Moreover, the inhibition of copper(II) is reversed by adding zinc(II), whereas the monovalent cations affect the enzyme activity irreversibly. The molecular basis of their action on the enzyme is also discussed on the basis of computational investigations.

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“…The tri-coordinated Hg(II) force-field parameters (Table 4) were used in the MD simulations of Hg(II)-bound Tn21 MerR. The force-field parameters for the linearly coordinated Cu(I) in CueR were previously derived from ab initio calculations, 59 and have been employed in MD simulations of the copper chaperones Atox1 and CopZ 60 .…”

Section: Force Field Parameterization Of Hg(ii) In Merrmentioning

confidence: 99%

“…Both K99T and K99Q are poor repressors in vivo. 23 These polar substitutes would neither repel nor attract, suggesting that an electrostatic interaction [57][58][59][60] between K99 and K99′ might constrain rotation around the coiled coil axis with consequent effects on the DNA binding domain. Freer inter-protomer roll in the absence of a putative electrostatic "clamp" might compromise tight contact of M106 with the hydrophobic residues in the α3-α4 turn region leading to unstable DNA contacts by α2.…”

mentioning

confidence: 99%

Integrating the Molecular Machines of Mercury Detoxification into Host Cell Biology

Summers¹

2010

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Metalloregulators of the MerR family activate transcription upon metal binding by underwinding the operator-promoter DNA to permit open complex formation by pre-bound RNA polymerase. Historically, MerR's allostery has been monitored only indirectly via nuclease sensitivity or by fluorescent nucleotide probes and was very specific for Hg(II), although purified MerR binds several thiophilic metals. To observe directly MerR's ligand-induced behavior we made 2-fluorotyrosine-substituted MerR and found similar, minor changes in 19 F chemical shifts of tyrosine residues in the free protein exposed to Hg(II), Cd(II) or Zn(II). However, DNA binding elicits large chemical shift changes in MerR's tyrosine residues and in DNAbound MerR Hg(II) provokes changes very distinct from those of Cd(II) or Zn(II). These chemical shift changes and other biophysical and phenotypic properties of wild-type MerR and relevant mutants reveal elements of an allosteric network that enables the coordination state of the metal binding site to direct metal-specific movements in the distant DNA binding site and the DNA-bound state also to affect the metal binding domain. IntroductionMetal homeostasis, the timely and specific movement of beneficial metal ions from outside the cell into their appropriate intracellular niches as structural or catalytic cofactors, is an essential process in all organisms, effected by membrane transporters and cytoplasmic metallochaperones controlled by metalloregulators.1 The molecular mechanisms enabling such proteins to make distinct responses to chemically similar metal ligands are just beginning to be elucidated, but recent work underscores the need for appropriately arranged protein ligands to support effective metal occupancy. [2][3][4] In addition to genes for homeostasis of beneficial metals, bacteria frequently have genes that afford survival of exposure to toxic metals; the transcriptional regulators of such metal resistance systems are often homologs of those managing homeostasis of essential metals. 5 One of the largest such metalloregulator families is named for the transcriptional repressor-activator of the bacterial mercury resistance (mer) operon, MerR, and includes CueR, ZntR, CoaR, PbrR, and SoxR that control bacterial resistance and/or homeostasis to Hg(II), Cu(I/II), Zn(II), Co(II) and Pb(II/III) and the Fe(II/III)-mediatedresponse to superoxide, respectively. There is a second distinct branch within the MerR family comprised of aromatic-compound-responsive regulators such as BmrR and Mta that control multidrug efflux pumps 5 ( Figure 1). In promoters regulated by MerR-family members, a dyadic operator lies within an overlong spacer between good consensus −10 and −35 recognition sites for the major cellular RNA polymerase. MerR bends its operator DNA (MerOP) 6,7 and surprisingly represses transcription of the structural genes merTPCAD by capturing RNA polymerase (RNAP) in a stable but inactive pre-initiation complex. [8][9][10][11] When Hg(II) binds to DNA-bound MerR, the protein underwinds the...

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New model potentials for sulfur–copper(I) and sulfur–mercury(II) interactions in proteins: From ab initio to molecular dynamics

Cited by 22 publications

References 62 publications

The Dual Carboxymethyl Cellulase and Gelatinase Activities of a Newly Isolated Protein from Brevibacillus agri ST15c10 Confer Reciprocal Regulations in Substrate Utilization

The Dual Carboxymethyl Cellulase and Gelatinase Activities of a Newly Isolated Protein from Brevibacillus agri ST15c10 Confer Reciprocal Regulations in Substrate Utilization

Copper(I) and Copper(II) Inhibit Aβ Peptides Proteolysis by Insulin‐Degrading Enzyme Differently: Implications for Metallostasis Alteration in Alzheimer’s Disease

Integrating the Molecular Machines of Mercury Detoxification into Host Cell Biology

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