Design of Zn-Binding Peptide(s) from Protein Fragments
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00619174" target="_blank" >RIV/61388963:_____/25:00619174 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1002/cbic.202401014" target="_blank" >https://doi.org/10.1002/cbic.202401014</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cbic.202401014" target="_blank" >10.1002/cbic.202401014</a>
Alternative languages
Result language
angličtina
Original language name
Design of Zn-Binding Peptide(s) from Protein Fragments
Original language description
We designed a minimalistic zinc(II)-binding peptide featuring the Cys(2)His(2) zinc-finger motif. To this aim, several tens of thousands of (His/Cys)-X-n-(His/Cys) protein fragments (n=2-20) were first extracted from the 3D protein structures deposited in Protein Data Bank (PDB). Based on geometrical constraints positioning two Cys (C) and two His (H) side chains at the vertices of a tetrahedron, approximately 22 000 sequences of the (H/C)-X-i-(H/C)-X-j-(H/C)-X-k-(H/C) type, satisfying Nmetal-binding H=Nmetal-binding C=2, were processed. Several other criteria, such as the secondary structure content and predicted fold stability, were then used to select the best candidates. To prove the viability of the computational design experimentally, three peptides were synthesized and subjected to isothermal calorimetry (ITC) measurements to determine the binding constants with Zn2+, including the entropy and enthalpy terms. For the strongest Zn2+ ions binding peptide, P1, the dissociation constant was shown to be in the nanomolar range (K-D=similar to 220 nM, corresponding to Delta G(bind)=-9.1 kcal mol(-1)). In addition, ITC showed that the [P1 : Zn2+] complex forms in 1 : 1 stoichiometry and two protons are released upon binding, which suggests that the zinc coordination involves both cysteines. NMR experiments also indicated that the structure of the [P1 : Zn2+] complex might be quite similar to the computationally predicted one. In summary, our proof-of-principle study highlights the usefulness of our computational protocol for designing novel metal-binding peptides.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GA23-05940S" target="_blank" >GA23-05940S: Catalytic Metallopeptides: Bridging the Gap Between Small Molecule Catalysts and Metalloenzymes</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chembiochem
ISSN
1439-4227
e-ISSN
1439-7633
Volume of the periodical
26
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
e202401014
UT code for WoS article
001432411900001
EID of the result in the Scopus database
2-s2.0-85218882852