PXD029712

PXD029712 is an original dataset announced via ProteomeXchange.

Title	AMOXICILLIN HAPTENATION OF α-ENOLASE
Description	Allergic reactions to antibiotics are a major concern in the clinic, with almost 15% of the patients presenting with adverse reactions against β-lactam antibiotics. One of the mechanisms involved in this outcome is the modification of proteins by covalent binding of the drug (haptenation). Hence, the interest in identifying the corresponding serum and cellular protein targets. Importantly, haptenation susceptibility and extent can be modulated by the context, including factors affecting protein conformation or the occurrence of other posttranslational modifications. We previously identified the glycolytic enzyme α-enolase as a target for haptenation by amoxicillin, both in cells and in the extracellular milieu. Here, we performed an in vitro study to analyze amoxicillin haptenation of α-enolase using gel-based and activity assays. Moreover, the possible interplay or interference of amoxicillin haptenation with acetylation was also studied in 1D- and 2D-gels that showed decreased haptenation and displacement of the haptenation signal to lower pI spots upon chemical acetylation, respectively. Mass spectrometry identified lysine 239 as the amoxicillin target residue on α enolase, thus suggesting a selective haptenation under our conditions. The amoxicillin binding site and the surrounding interactions were investigated using the α-enolase crystal structure and molecular docking. Altogether, the results obtained provide the basis for the design of novel diagnostic tools or approaches in the study of amoxicillin-induced allergic reactions.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_09:00:40.478.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandra Altomare
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-12 06:07:15	ID requested
⏵ 1	2022-02-17 09:00:41	announced

Gonz, á, lez-Morena JM, S, á, nchez-G, ó, mez FJ, Vida Y, P, é, rez-Inestrosa E, Salas M, Monta, ñ, ez MI, Altomare A, Aldini G, Pajares MA, P, é, rez-Sala D, -Enolase is Modulated by Active Site Occupancy and Acetylation. Front Pharmacol, 12():807742(2021) [pubmed]

submitter keyword: β-lactam antibiotics

protein modification by drugs

mass spectrometry

posttranslational modifications

acetylation

allergic responses to drugs

Alessandra Altomare
contact affiliation	Bio-pharmaceutical Analysis Lab; Department of Pharmaceutical Science; University of Milan; Milan, Italy
contact email	alessandra.altomare@unimi.it
lab head
Alessandra Altomare
contact affiliation	University of Milan (DISFARM)
contact email	alessandra.altomare@unimi.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD029712

PRIDE project URI

• PRIDE
  1. PXD029712
     1. Label: PRIDE project
     2. Name: AMOXICILLIN HAPTENATION OF α-ENOLASE