Semenogelins armed in Zn(II) and Cu(II): may bioinorganic chemistry help nature to cope with Enterococcus faecalis?

Antimicrobial fragments of semenogelinsfrom the human semen(peptides: SgIIA, SgI-29, and their common 15 amino acid fragment,Sg-15) bind Zn(II) and Cu(II) ions via a [NH2, 3Nim] donorset at physiological pH, and metal binding enhances their antimicrobialactivity. In the case of the two native semenogelin fragment metalcomplexes, the strong local positive charge in the metal-bound HHmotif correlates well with their antimicrobial activity.Proteolytic degradation of semenogelins, the most abundantproteinsfrom human semen, results in the formation of 26- and 29-amino acidpeptides (SgIIA and SgI-29, respectively), which share a common 15amino acid fragment (Sg-15). All three ligands are effective Zn(II)and Cu(II) binders; in solution, a variety of differently metalatedspecies exist in equilibrium, with the [NH2, 3N(im)] donor set prevailing at physiological pH in the case of both metals.For the first time, the Cu(II)-induced antimicrobial activity of Sg-15against Enterococcus faecalis is shown. In the caseof the two native semenogelin fragment metal complexes, the stronglocal positive charge in the metal-bound HH motif correlates wellwith their antimicrobial activity. A careful analysis of semenogelins'metal coordination behavior reveals two facts: (i) The histamine-likeCu(II) binding mode of SgI-29 strongly increases the stability ofsuch a complex below pH 6 (with respect to the non-histamine-likebinding of SgIIA), while in the case of the SgI-29 Zn(II)-histamine-likespecies, the stability enhancement is less pronounced. (ii) The HHsequence is a more tempting site for Cu(II) ions than the HXH one

How copper ions and membrane environment influence the structure of the human and chicken tandem repeats domain?

Prion proteins (PrPs) from different species have the enormous ability to anchor copper ions. The N-terminal domain of human prion protein (hPrP) contains four tandem repeats of the –PHGGGWGQ– octapeptide sequence. This octarepeat domain can bind up to four Cu 2+ ions. Similarly to hPrP, chicken prion protein (chPrP) is able to interact with Cu 2+ through the tandem hexapeptide -HNPGYP- region (residues 53–94). In this work, we focused on the human octapeptide repeat (human Octa 4 , hPrP 60–91 ) (Ac-PHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQ-NH 2 ) and chicken hexapeptide repeat (chicken Hexa 4 , chPrP 54–77 ) (Ac-HNPGYPHNPGYPHNPGYPHNPGYP-NH 2 ) prion protein fragments. Due to the fact that PrP is a membrane-anchored glycoprotein and its unstructured and flexible N-terminal domain may interact with the lipid bilayer, our studies were carried out in presence of the surfactant sodium dodecyl sulfate (SDS) mimicking the membrane environment in vitro. The main objective of this work was to understand the effects of copper ion on the structural rearrangements of the human and chicken N-terminal repeat domain. The obtained results provide a fundamental first step in describing the thermodynamic (potentiometric titrations) and structural properties of Cu(II) binding (UV–Vis, NMR, CD spectroscopy) to both human Octa 4 and chicken Hexa 4 repeats in both a DMSO/water and SDS micelle environment. Interestingly, in SDS environment, both ligands indicate different copper coordination modes, which results of the conformational changes in micelle environment. Our results strongly support that copper binding mode strongly depends on the protein backbone structure. Moreover, we focused on previously obtained results for amyloidogenic human and chicken fragments in membrane mimicking environment

Metal specificity of the Ni(ii) and Zn(ii) binding sites of the N-terminal and G-domain ofE. coliHypB

HypB is one of the chaperones required for proper nickel insertion into [NiFe]-hydrogenase.Escherichia coliHypB has two potential Ni(ii) and Zn(ii) binding sites—the N-terminal one and the so-called GTPase one. The metal-loaded HypB-SlyD metallochaperone complex activates nickel release from the N-terminal HypB site. In this work, we focus on the metal selectivity of the two HypB metal binding sites and show that (i) the N-terminal region binds Zn(ii) and Ni(ii) ions with higher affinity than the G-domain and (ii) the lower affinity G domain binds Zn(ii) more effectively than Ni(ii). In addition, the high affinity N-terminal domain, both in water and membrane mimicking SDS solution, has a larger affinity towards Zn(ii) than Ni(ii), while an opposite situation is observed at basic pH; at pH 7.4, the affinity of this region towards both metals is almost the same. The N-terminal HypB region is also more effective in Ni(ii) binding than the previously studied SlyD metal binding regions. Considering that the nickel chaperone SlyD activates the release of nickel and blocks the release of zinc from the N-terminal high-affinity metal site of HypB, we may speculate that such pH-dependent metal affinity might modulate HypB interactions with SlyD, being dependent on both pH and the protein's metal status

Uncapping the N-terminus of a ubiquitous His-tag peptide enhances its Cu²⁺ binding affinity

Copper(ii) complexes with the studied His-rich motif are polymorphic, exhibit a 3–10 helix, and are more stable than a His6-tag complex.</p

Structural analysis of copper(I) interaction with amyloid β peptide

The N-terminal fragment of Aβ (β = beta) peptide is able to bind essential transition metal ions like, copper, zinc and iron. Metal binding usually occurs via the imidazole nitrogens of the three His residues which play a key role in the coordination chemistry. Among all the investigated systems, the interaction between copper and Amyloid β assume a biological relevance because of the interplay between the two copper oxidation states, Cu(II) and Cu(I), and their involvement in redox reactions. Both copper ions share the ability to bind Amyloid β. A huge number of investigations have demonstrated that Cu(II) anchors to the N-terminal amino and His6, His13/14 imidazole groups, while Cu(I) forms a linear complex by coordinating to the His13 and His14 dyad. In this study we have analyzed Cu(I) interaction with the Amyloid β fragment encompassing the first 16 amino-acids. Our data were obtained by means of NMR spectroscopy which provided relevant structural details of the metal complexes. Our findings are consistent with the involvement of two or three His in the Cu(I) coordination sphere and indicate that His6 effectively participates to the metal binding