How E-, L-, and P-Selectins Bind to sLe(x) and PSGL-1: A Quantification of Critical Residue Interactions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F23%3A00131650" target="_blank" >RIV/00216224:14110/23:00131650 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jcim.3c00704" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jcim.3c00704</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.3c00704" target="_blank" >10.1021/acs.jcim.3c00704</a>

Result language

angličtina

Original language name

How E-, L-, and P-Selectins Bind to sLe(x) and PSGL-1: A Quantification of Critical Residue Interactions

Original language description

Selectins and their ability to interact with specific ligands are a cornerstone in cell communication. Over the last three decades, a considerable wealth of experimental and molecular modeling insights into their structure and modus operandi were gathered. Nonetheless, explaining the role of individual selectin residues on a quantitative level remained elusive, despite its importance in understanding the structure-function relationship in these molecules and designing their inhibitors. This work explores essential interactions of selectin-ligand binding, employing a multiscale approach that combines molecular dynamics, quantumchemical calculations, and residue interaction network models. Such an approach successfully reproduces most of the experimental findings. It proves to be helpful, with the potential for becoming an established tool for quantitative predictions of residue contribution to the binding of biomolecular complexes. The results empower us to quantify the importance of particular residues and functional groups in the protein-ligand interface and to pinpoint differences in molecular recognition by the three selectins. We show that mutations in the E-, L-, and P-selectins, e.g., different residues in positions 46, 85, 97, and 107, present a crucial difference in how the ligand is engaged. We assess the role of sulfation of tyrosine residues in PSGL-1 and suggest that TyrSO3- in position 51 interacting with Arg85 in P-selectin is a significant factor in the increased affinity of P-selectin to PSGL-1 compared to E- and L-selectins. We propose an original pharmacophore targeting five essential PSGL-binding sites based on the analysis of the selectin center dot center dot center dot PSGL-1 interactions.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

1549-960X

Volume of the periodical

63

Issue of the periodical within the volume

17

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

5604-5618

UT code for WoS article

001032527500001

EID of the result in the Scopus database

2-s2.0-85167829739