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.
Dudek, D., Miller, A., Hecel, A., Kola, A., Valensin, D., Mikolajczyk, A., et al. (2023). Semenogelins armed in Zn(II) and Cu(II): may bioinorganic chemistry help nature to cope with Enterococcus faecalis?. INORGANIC CHEMISTRY, 62(34), 14103-14115 [10.1021/acs.inorgchem.3c02390].
Semenogelins armed in Zn(II) and Cu(II): may bioinorganic chemistry help nature to cope with Enterococcus faecalis?
Kola, A;Valensin, D;
2023-01-01
Abstract
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.File | Dimensione | Formato | |
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https://hdl.handle.net/11365/1253874