PXD007913

PXD007913 is an original dataset announced via ProteomeXchange.

Title	Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug Metaboing Enzymes as a Response to Redox Alteration
Description	The lumen of the endoplasmic reticulum (ER) provides an oxidizing environment to aid in the formation of disulfide bonds, which is tightly regulated by both antioxidant proteins and small molecules. On the cytoplasmic side of the ER, cytochrome P450 (P450) proteins have been identified as a superfamily of enzymes that are important in the formation of endogenous chemicals as well as in the detoxication of xenobiotics. Our previous report described oxidative inhibition of P450 Family 4 enzymes via oxidation of the heme-thiolate cysteine to a sulfenic acid (-SOH) (Albertolle, M. E. et al. (2017) J. Biol. Chem. 292, 11230-11242). Further proteomic analyses of murine kidney and liver microsomes led to the finding that a number of other drug metabolizing enzymes located in the ER are also redox-regulated in this manner. We expanded our analysis of sulfenylated enzymes to human liver and kidney microsomes. Evaluation of the sulfenylation, catalytic activity, and spectral properties of P450s 1A2, 2C8, 2D6, and 3A4 led to the identification of two classes of redox sensitivity in P450 enzymes: heme thiolate-sensitive and thiol-insensitive. These findings provide evidence for a mammalian P450 regulatory mechanism, which may also be relevant to other drug-metabolizing enzymes.
HostingRepository	PRIDE
AnnounceDate	2018-03-01
AnnouncementXML	Submission_2018-03-01_05:12:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Albertolle
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	dihydroxylated residue; L-cysteine sulfenic acid
Instrument	LTQ Orbitrap XL; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-09 01:45:04	ID requested
⏵ 1	2018-03-01 05:12:45	announced

Albertolle ME, Phan TTN, Pozzi A, Guengerich FP, Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug-Metabolizing Enzymes as a Response to Redox Alteration. Mol Cell Proteomics, 17(5):889-900(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Human, Mouse, Sulfenic Acid, Redox Proteomics, Dimedone

F. Peter Guengerich
contact affiliation	Tadashi Inagami Professor of Biochemistry Dept. of Biochemistry Vanderbilt University School of Medicine
contact email	f.guengerich@vanderbilt.edu
lab head
Matthew Albertolle
contact affiliation	Vanderbilt University
contact email	matt.albertolle@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007913
     1. Label: PRIDE project
     2. Name: Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other Drug Metaboing Enzymes as a Response to Redox Alteration