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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologie pro budoucnost</a><br>

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY

ISSN

1044-0305

e-ISSN

—

Svazek periodika

32

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1041-1052

Kód UT WoS článku

000639017300021

EID výsledku v databázi Scopus

2-s2.0-85103478039