PXD006483

PXD006483 is an original dataset announced via ProteomeXchange.

Title	Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics
Description	Pyridoxal phosphate (PLP) is an enzyme cofactor required for the chemical transformation of biological amines in numerous essential cellular processes. PLP-dependent enzymes (PLP-DEs) are ubiquitous and evolutionarily diverse, making their classification based on sequence homology challenging. This calls for a more direct approach for identifying new PLP-DEs and uncovering novel roles of PLP within the cell. We present a chemical proteomic method for reporting on PLP-DEs using functionalized cofactor probes. PL-analogs designed to be taken up by cells and metabolized in situ were synthesized. The probes are phosphorylated to functional cofactor surrogates by cellular PL kinases and bind to PLP-DEs via a reversible aldimine bond, which can be fixed by NaBH4-reduction. Conjugation to a reporter tag permits the identification of PLP-DEs using quantitative, label-free mass spectrometry via confidence ranking and profile searches. We label a significant portion of the PLP-ome in Staphylococcus aureus (41%) and annotate uncharacterized proteins as novel PLP-DEs. In applying our method, we were able to study structural tolerance within PLP-DE active sites and to screen for off-targets of the PLP-DE inhibitor D-cycloserine. Our cofactor profiling method represents a robust way to mine the cellular inventory of PLP-DEs which can be used for genome annotation, comparative profiling and drug development.
HostingRepository	PRIDE
AnnounceDate	2018-10-17
AnnouncementXML	Submission_2018-10-17_07:35:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nina Bach
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-10 04:14:44	ID requested
⏵ 1	2018-10-17 07:35:15	announced

Hoegl A, Nodwell MB, Kirsch VC, Bach NC, Pfanzelt M, Stahl M, Schneider S, Sieber SA, Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics. Nat Chem, 10(12):1234-1245(2018) [pubmed]

curator keyword: Biological

submitter keyword: Pyridoxal phosphate, cofactor, vitamin B6

Prof. Stephan A. Sieber
contact affiliation	TU München Lehrstuhl Organische Chemie II Department of Chemistry Lichtenbergstr. 4 85747 Garching bei München
contact email	stephan.sieber@tum.de
lab head
Nina Bach
contact affiliation	TU München
contact email	nina.bach@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006483
     1. Label: PRIDE project
     2. Name: Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics