A minimalist chemical model of matrix metalloproteinases — Can small peptides mimic the more rigid metal binding sites of proteins?

Abstract

In order to develop a minimalist chemical model of matrix metalloproteinases (MMPs), we Around pH 6-7 the peptide, similarly to MMPs, offers {3N im } coordinated binding site for both zinc(II) and copper(II). In the case of copper(II), the formation of amide coordinated species at higher pH ceased the analogy with the copper(II) containing MMP variant. On the other hand, the zinc(II)-peptide system mimics some basic features of the MMP active sites: the main species around pH 7 (ZnH 2 L) possesses {3N im ,H 2 O} coordination environment, the deprotonation of the zinc-bound water takes place near to the physiological pH, it forms relatively stable ternary complexes with hydroxamic acids, and the species ZnH 2 L(OH) and ZnH 2 L(OH) 2 have notable hydrolytic activity between pH 7-9.

Copper(II) and nickel(II) binding sites of peptide containing adjacent histidyl residues

“…Spectrum 2.d shows a broadly unresolved spectra which can be recorded in the presence of excess copper(II) ions and above pH~8.0. This spectrum indicate the presence of dinuclear complexes in which two paramagnetic metal ions are close enough to interact as it was also suggested in various literature reports [33,34]. Moreover, the formation of both mono-and di-nuclear complexes was also proved by ESI MS measurements.…”

Designing Hydrolytic Zinc Metalloenzymes

“…Then we will discuss a design study involving the related MMPs, which, like CA, have a ZnHis 3 (H 2 O) active center. 103 We will then discuss the more extensive redesign approach of an enzyme, glyoxolase II, structurally unrelated to CA and MMP but that still performs hydrolytic catalysis. 104 Finally, we will discuss the redesign of native zinc proteins, which are not initially catalytic but have mononuclear structural zinc sites.…”

Tuning the coordination properties of multi-histidine peptides by using a tripodal scaffold: solution chemical study and catechol oxidase mimicking

“…[8][9][10][11][12] Previously, we also studied some histidine-rich peptides in order to create similar metal ion environment to native enzymes. 1,6,[8][9][10][11] Such metallopeptides may possess notable catalytic activity to promote either hydrolytic 8,14 or redox [9][10][11][12][13] reactions. However, from structural point of view, linear peptides may only be useful to mimic metal binding sites of native enzymes, if the residues involved in the coordination are part of a relatively short sequence.…”