Accéder au contenu
Merck

Quantitative reactivity profiling predicts functional cysteines in proteomes.

Nature (2010-11-19)
Eranthie Weerapana, Chu Wang, Gabriel M Simon, Florian Richter, Sagar Khare, Myles B D Dillon, Daniel A Bachovchin, Kerri Mowen, David Baker, Benjamin F Cravatt
RÉSUMÉ

Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here we describe a proteomics method to profile quantitatively the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyper-reactivity was a rare feature among cysteines and it was found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and is involved in iron-sulphur protein biogenesis. We also demonstrate that quantitative reactivity profiling can form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
MSBT-alkyne, ≥95%
Sigma-Aldrich
BMK-alkyne
Sigma-Aldrich
MI-alkyne, ≥95%
Sigma-Aldrich
MSOD-alkyne, ≥95%
Sigma-Aldrich
AlkFAA-alkyne, ≥95%
Sigma-Aldrich
EBX2-alkyne, ≥95%
Sigma-Aldrich
PFPSA-alkyne, ≥95%
Sigma-Aldrich
BrBT-alkyne, ≥95%
Sigma-Aldrich
AlkVSA-alkyne, ≥95%
Sigma-Aldrich
ArVS-alkyne, ≥95%
Sigma-Aldrich
CA-alkyne, ≥95%
Sigma-Aldrich
ArVSA-alkyne, ≥95%
Sigma-Aldrich
MST-alkyne, ≥95%
Sigma-Aldrich
CA-nitrile, ≥95%
Sigma-Aldrich
EBX1-alkyne, ≥95.0%