Probing D- and L-Adrenaline Binding to beta(2)-Adrenoreceptor Peptide Motifs by Gas-Phase Photodissociation Cross-Linking and Ion Mobility Mass Spectrometry

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F21%3A73609475" target="_blank" >RIV/61989592:15310/21:73609475 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/jasms.1c00019" target="_blank" >https://pubs.acs.org/doi/10.1021/jasms.1c00019</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jasms.1c00019" target="_blank" >10.1021/jasms.1c00019</a>

Result language

angličtina

Original language name

Probing D- and L-Adrenaline Binding to beta(2)-Adrenoreceptor Peptide Motifs by Gas-Phase Photodissociation Cross-Linking and Ion Mobility Mass Spectrometry

Original language description

Diazirine-tagged D- and L-adrenaline derivatives formed abundant noncovalent gas-phase ion complexes with peptides N-Ac-SSIVSFY-NH2 (peptide S) and N-Ac-VYILLNW-IGY-NH2 (peptide V) upon electrospray ionization. These peptide sequences represent the binding motifs in the beta(2)-adrenoreceptor. The structures of the gas-phase complexes were investigated by selective laser photodissociation of the diazirine chromophore at 354 nm, which resulted in a loss of N-2 and formation of a transient carbene intermediate in the adrenaline ligand without causing its expulsion. The photolyzed complexes were analyzed by collision-induced dissociation (CID-MS3 and CID-MS4) in an attempt to detect cross-links and establish the binding sites. However, no cross-linking was detected in the complexes regardless of the peptide and D- or L-configuration in adrenaline. Cyclic ion mobility measurements were used to obtain collision cross sections (CCS) in N-2 for the peptide S complexes. These showed identical values, 334 +/- 0.9 angstrom(2), for complexes of the L- and D-adrenaline derivatives, respectively. Identical CCS were also obtained for peptide S complexes with natural L- and D-adrenaline, 317 +/- 1.2 angstrom(2), respectively. Born-Oppenheimer molecular dynamics (BOMD) in combination with full geometry optimization by density functional theory calculations provided structures for the complexes that were used to calculate theoretical CCS with the ion trajectory method. A close match (337 angstrom(2)) was found for a single low Gibbs energy structure that displayed a binding pocket with Ser 2 and Ser 5 residues forming hydrogen bonds to the adrenaline catechol hydroxyls. Analysis of the BOMD trajectories revealed a small number of contacts between the incipient carbene carbon atom in the ligand and X-H bonds in the peptide, which was consistent with the lack of cross-linking. Temperature dependence of the internal dynamics of peptide S-adrenaline complexes as well as the specifics of the adrenaline carbene reactions are discussed. In particular, peptide amide hydrogen transfer to the carbene carbon atom was calculated to require crossing a potential energy barrier, which may hamper cross-linking in competition with carbene internal rearrangements.

Czech name

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Czech description

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Type

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

CEP classification

—

OECD FORD branch

10406 - Analytical chemistry

Project

<a href="/en/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologies for Future</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2021

Confidentiality

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

Name of the periodical

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY

ISSN

1044-0305

e-ISSN

—

Volume of the periodical

32

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

1041-1052

UT code for WoS article

000639017300021

EID of the result in the Scopus database

2-s2.0-85103478039