Matić, Antonia; Šupljika, Filip; Brkić, Hrvoje; Jurasović, Jasna; Karačić, Zrinka; Tomić, Sanja (2023) Identification of an Additional Metal-Binding Site in Human Dipeptidyl Peptidase III. International Journal of Molecular Sciences, 24 (16). ISSN 1422-0067
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Abstract
Dipeptidyl peptidase III (DPP III, EC 3.4.14.4) is a monozinc metalloexopeptidase that hydrolyzes dipeptides from the N-terminus of peptides consisting of three or more amino acids. Recently, DPP III has attracted great interest from scientists, and numerous studies have been conducted showing that it is involved in the regulation of various physiological processes. Since it is the only metalloenzyme among the dipeptidyl peptidases, we considered it important to study the process of binding and exchange of physiologically relevant metal dications in DPP III. Using fluorimetry, we measured the Kd values for the binding of Zn2+, Cu2+, and Co2+ to the catalytic site, and using isothermal titration calorimetry (ITC), we measured the Kd values for the binding of these metals to an additional binding site. The structure of the catalytic metal's binding site is known from previous studies, and in this work, the affinities for this site were calculated for Zn2+, Cu2+, Co2+, and Mn2+ using the QM approach. The structures of the additional binding sites for the Zn2+ and Cu2+ were also identified, and MD simulations showed that two Cu2+ ions bound to the catalytic and inhibitory sites exchanged less frequently than the Zn2+ ions bound to these sites.
| Item Type: | Article | ||||||||
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| Uncontrolled Keywords: | binding affinity; dipeptidyl peptidase III; metal exchange; metal inhibition; metal ions | ||||||||
| Subjects: | NATURAL SCIENCES > Chemistry INTERDISCIPLINARY AREAS OF KNOWLEDGE |
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| Divisions: | Division of Organic Chemistry and Biochemistry | ||||||||
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| Depositing User: | Antonia Matić | ||||||||
| Date Deposited: | 16 Jan 2025 15:46 | ||||||||
| URI: | http://fulir.irb.hr/id/eprint/9481 | ||||||||
| DOI: | 10.3390/ijms241612747 |
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