Chemical "Butterfly Effect" Explaining the Coordination Chemistry and Antimicrobial Properties of Clavanin Complexes.

Magdalena Rowińska-Żyrek,Robert Wieczorek,Adriana Miller,Agnieszka Matera-Witkiewicz,Aleksandra Mikołajczyk

doi:10.1021/acs.inorgchem.1c02101

Magdalena Rowińska-Żyrek, Robert Wieczorek + Show 3 more

Open Access

https://doi.org/10.1021/acs.inorgchem.1c02101

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Abstract

Can a minor difference in the nonmetal binding sequence of antimicrobial clavanins explain the drastic change in the coordination environment and antimicrobial efficiency? This study answers the question with a definite “yes”, showing the details of the bioinorganic chemistry of Zn(II) and Cu(II) complexes with clavanins, histidine-rich, antimicrobial peptides from hemocytes of the tunicate Styela clava.

Highlights

Binding, and such a structural rearrangement of the metal binding site leads to a remarkable enhancement of the microbiological properties of the Zn(II)-clavanin C complex against a variety of pathogens
At pH 5.5, they inhibit the growth of Gram-positive (Listeria monocytogenes, MRSA), Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae), and fungi (Candida albicans),[11,15] triggering ongoing studies focused on their use as biofilm-preventing agents[16] or in bacterial biosensors.[17]
It was emphasized that in the case of clavanin A at pH 5.5, His[17] is crucial for both the peptide’s antimicrobial activity and its zinc(II) binding ability; in the α-helical conformation, His[17] and His[21] are expected to be present on the same side of the helix (i and i + 4 sites), and this HXXXH motif was suggested to be the primary Zn(II) anchoring site.[15]. Such a motif is typical for Zn(II)-based nucleases,[21] and among the six different clavanin sequences (Figure 1), only four contain the HXXXH pattern

Summary

Introduction

Binding, and such a structural rearrangement of the metal binding site leads to a remarkable enhancement of the microbiological properties of the Zn(II)-clavanin C complex against a variety of pathogens. Terminal deamidation [the free carboxylate group could be an additional Zn(II) binding site; studies find that the presence of the C-terminal amide group in an AMP can sometimes reduce its antimicrobial properties27] on the antimicrobial activity of clavanins and their metal complexes and to perform the studies at physiological pH (7.4), which may be most interesting for possible future applications.

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