Protein carbonylation represents one of the most important oxidative-based modifications involving nucleophilic amino acids and affecting protein folding and function. Protein carbonylation is induced by electrophilic carbonyl species and is an highly selective process since few nucleophilic residues are carbonylated within each protein. While considering the great interest for protein carbonylation, few studies investigated the factors which render a nucleophilic residue susceptible to carbonylation. Hence, the present study is aimed to delve into the factors which modulate the reactivity of cysteine, histidine and lysine residues towards α,β unsaturated carbonyls by a retrospective analysis of the available studies which identified the adducted residues for proteins, the structure of which was resolved. Such an analysis involved different parameters including exposure, nucleophilicity, surrounding residues and capacity to attract carbonyl species (as derived by docking simulations). The obtained results allowed a meaningful clustering of the analyzed proteins suggesting that on average carbonylation selectivity increases with protein size. The comparison between adducted and unreactive residues revealed differences in all monitored parameters which are markedly more pronounced for cysteines compared to lysines and histidines. Overall, these results suggest that cysteine's carbonylation is a finely (and reasonably purposely) modulated process, while the carbonylation of lysines and histidines seems to be a fairly random event in which limited differences influence their reactivity.

Key factors regulating protein carbonylation by α,β unsaturated carbonyls : a structural study based on a retrospective meta-analysis / G. Vistoli, C. Mantovani, S. Gervasoni, A. Pedretti, G. Aldini. - In: BIOPHYSICAL CHEMISTRY. - ISSN 0301-4622. - 230(2017 Nov), pp. 20-26. [10.1016/j.bpc.2017.08.002]

Key factors regulating protein carbonylation by α,β unsaturated carbonyls : a structural study based on a retrospective meta-analysis

G. Vistoli
Primo
;
S. Gervasoni;A. Pedretti
Penultimo
;
G. Aldini
Ultimo
2017-11

Abstract

Protein carbonylation represents one of the most important oxidative-based modifications involving nucleophilic amino acids and affecting protein folding and function. Protein carbonylation is induced by electrophilic carbonyl species and is an highly selective process since few nucleophilic residues are carbonylated within each protein. While considering the great interest for protein carbonylation, few studies investigated the factors which render a nucleophilic residue susceptible to carbonylation. Hence, the present study is aimed to delve into the factors which modulate the reactivity of cysteine, histidine and lysine residues towards α,β unsaturated carbonyls by a retrospective analysis of the available studies which identified the adducted residues for proteins, the structure of which was resolved. Such an analysis involved different parameters including exposure, nucleophilicity, surrounding residues and capacity to attract carbonyl species (as derived by docking simulations). The obtained results allowed a meaningful clustering of the analyzed proteins suggesting that on average carbonylation selectivity increases with protein size. The comparison between adducted and unreactive residues revealed differences in all monitored parameters which are markedly more pronounced for cysteines compared to lysines and histidines. Overall, these results suggest that cysteine's carbonylation is a finely (and reasonably purposely) modulated process, while the carbonylation of lysines and histidines seems to be a fairly random event in which limited differences influence their reactivity.
4-hydroxy-trans‑2-nonenal; docking simulations;protein carbonylation; reactive carbonyl species; residue nucleophilicity; amino acids; animals; databases, factual; humans; hydrogen bonding; molecular docking simulation; oxidative stress; protein carbonylation; proteins; biophysics; biochemistry; organic chemistry
Settore CHIM/08 - Chimica Farmaceutica
Article (author)
File in questo prodotto:
File Dimensione Formato  
Biophys.Chem._230-2017.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 925.22 kB
Formato Adobe PDF
925.22 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/554591
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact