{"database":"MassIVE","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v03/MSV000086546/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"submitter":["Kebing Yu"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=b39543ba6178435985e74f748705bd1f"],"submitter_email":["yu.kebing@gene.com"],"sample_protocol":[""],"repository":["MassIVE"],"file_size":["46"],"ptm_modification":["UNIMOD:4 - \"Iodoacetamide derivative.\"","UNIMOD:35 - \"Oxidation or Hydroxylation.\""],"data_protocol":[""],"omics_type":["Proteomics"],"instrument_platform":["Orbitrap Fusion Lumos","Orbitrap Fusion"],"species":["Homo Sapiens (ncbitaxon:9606)"],"submitter_affiliation":["Genentech"],"pubmed_abstract":["Recent advances in targeted covalent inhibitors have aroused significant interest for their potential in drug development for difficult therapeutic targets. Proteome-wide profiling of functional residues is an integral step of covalent drug discovery aimed at defining actionable sites and evaluating compound selectivity in cells. A classical workflow for this purpose is called IsoTOP-ABPP, which employs an activity-based probe and two isotopically labeled azide-TEV-biotin tags to mark, enrich, and quantify proteome from two samples. Here we report a novel isobaric 11plex-AzidoTMT reagent and a new workflow, named AT-MAPP, that significantly expands multiplexing power as compared to the original isoTOP-ABPP. We demonstrate its application in identifying cysteine on- and off-targets using a KRAS G12C covalent inhibitor ARS-1620. However, changes in some of these hits can be explained by modulation at the protein and post-translational levels. Thus, it would be crucial to interrogate site-level bona fide changes in concurrence to proteome-level changes for corroboration. In addition, we perform a multiplexed covalent fragment screening using four acrylamide-based compounds as a proof-of-concept. This study identifies a diverse set of liganded cysteine residues in a compound-dependent manner with an average hit rate of 0.07% in intact cell. Lastly, we screened 20 sulfonyl fluoride-based compounds to demonstrate that the AT-MAPP assay is flexible for noncysteine functional residues such as tyrosine and lysine. Overall, we envision that 11plex-AzidoTMT will be a useful addition to the current toolbox for activity-based protein profiling and covalent drug development."],"pubmed_title":["AzidoTMT Enables Direct Enrichment and Highly Multiplexed Quantitation of Proteome-Wide Functional Residues."],"pubmed_authors":["Ma Taylur P TP, Izrael-Tomasevic Anita A, Mroue Rana R, Budayeva Hanna H, Malhotra Sushant S, Raisner Ryan R, Evangelista Marie M, Rose Christopher M CM, Kirkpatrick Donald S DS, Yu Kebing K"],"name_synonyms":["total expressed protein, wide, wide/broad, Activity, broad., General activity, Proteomes"],"description_synonyms":["ACMICD, OCTD, Svc, Manuscripts., Bru, Col4a-1, Raw, ECTOL1, SSKS, FBN, MFS1, Del(8)44H, MASS, GPHYSD2, WMS, WMS2, SGS"],"pubmed_title_synonyms":["total expressed protein, wide, wide/broad, broad., Proteomes"],"pubmed_abstract_synonyms":["Amyloid intracellular domain 57, Amyloid intracellular domain 59, para Tyrosine, Prospecting, Lysine Hydrochloride, A4, Progress Reports, Pharmaceutical Development, Amyloid intracellular domain 50, DmelCG8201, AAA, 5730420M11Rik, Cvap, dmTAF[[II]]230, Personal, protein polypeptide chains, ras, Lysine Acetate, AG, Biotin, Summary Report, GRP1, Grp1, 2, 2-amino-3-mercaptopropanoic acid, Work Flow, AID(50), C-K-RAS, L Lysine, average, C, SET, Ag, TFIID TAF250, Progress Report, cel, K, PTPSTEP, 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, cis-Hexahydro-2-oxo-1H-thieno(3, Fluoride, proteins, Y, Alzheimer disease amyloid A4 protein homolog, Social, DmelCG4299, N-APP, set, Gamma-secretase C-terminal fragment 50, Field Reports, LYS, Gamma-secretase C-terminal fragment 57, scientific observation, Gamma-secretase C-terminal fragment 59, Lysin, AD1, Social Power, Half Cystine, Azide, GPH, Power, dTAF[[II]]230, Rombellin, S-APP-alpha, Zinc Cysteinate, TAF200, dMARK, para-Tyrosine, CG11960, (3aS-(3aalpha, CG30131, CG30132, EMK, Workflows, Prediction, DPAR-1, (2R)-2-amino-3-sulfanylpropanoic acid, Target Prediction, Cerebral vascular amyloid peptide, 1H-Thieno(3, HLA-DR-associated protein II, DI-2, CG11628, I-2Dm, Field, reagent, Striatum-enriched protein-tyrosine phosphatase, alpha, Akrylamid, L isomer, I-2PP1, Report, TAF-IBETA, antagonists and inhibitors, RASK2, Taf250, BcDNA:RH48823, Indicator, TAF-Ibeta, L-Tyrosine, D-(+)-biotin, Biokur, Work Flows, 1-(4-(6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)prop-2-en-1-one sulfane, TAF230, Psychological Power, Drug Target Predictions., Deacura, GRP1/cytohesin 1, Par-1c, Medebiotin, L-Zystein, betaApp, protein-containing complex, CG11633, AID(59), Gene Products, Kras-2, Lysine, Half-Cystine, Gelfert, Biotin Hermes, 27C1, dTAF[[II]]250, PreA4, cell, L Cysteine, E-920, K-RAS4B, K-RAS4A, S-APP-beta, 2pp2a, Hcys, Gamma-CTF(59), CG10574, dTAF250, AID(57), 4-d]imidazole-4-valeric acid, PAR-1, 2PP2A, CYSTEINE, Par-1, dSET, dSet, FREE CYSTEINE, Tyrosin, (2R)-2-amino-3-mercaptopropanoic acid, Investigative Reports, inhibitors, measuring, Amyloidogenic glycoprotein, K-RAS2B, K-RAS2A, Proteins, Roche, stepk, BG:DS00004.13, c-Ki-ras, Cell, dTAF230, Discovery, native protein, I-2PP2A, tirosina, Acetate, Research Reports, Dm I-2, chemical analysis, TAF[[II]]250/230, 2-Propenamide, L-Lysine, Drug Target Predictions, Taf[[II]]250, NS, Gabunat, ensemble, (R)-2-amino-3-mercaptopropanoic acid, 4)imidazole-4-valeric acid, 2-Amino-3-mercaptopropionic acid, DmelCG11628, C31, Gene Proteins, Reports, Isolation of Nuclei TAgged in specific Cell Types, Power (Psychology), DPar1, E920, PN2, Beta-APP42, Beta-APP40, General activity, Enisyl, ABPP, APP, ABETA, IPP2A2, Par1c, E 920, Activity, vitamin B7, determination, CTFgamma, protein, Abpp, ethylenecarboxamide, Beta-amyloid protein 42, Drug Prospecting, Beta-amyloid protein 40, 6aR)-Hexahydro-2-oxo-1H-thieno[3, Cystein, protein aggregate, Summary Reports, k-ras, rask2, Psychological, mAPP, TAF-I, cisteina, (3aS, biotina, epsilon-diaminocaproic acid, biotine, Progress, IGAAD, Hermes, DmelCG10574, Pharmaceutical, l(2)k08110, Tyr, Abeta, APPI, biotinum, Reagents, C80, CG16701, reagents, C83, phapii, Medobiotin, wide/broad, CG8201, AICD-50, Ki-ras, 2-Amino-3-(p-hydroxyphenyl)propionic acid, StF-IT-1, Psychological Powers, TAFII-250, Gamma-CTF(57), TAF250/230, Cys, 4S, 4-d)imidazole-4-pentanoic acid, Tyrosine, C99, TAFII250, Investigative Report, p21, 3.1.3.48, AICD-57, lysine, Biotin Ratiopharm, 4-d)imidazoline-4-valeric acid, reactif, region, AICD-59, D-Biotin, Biotine Roche, Step, L-isomer, L-Cysteine, CG4299, Alzheimer disease amyloid protein, Protease nexin-II, CG17603, TAF[[II]], L-Cystein, wide, l(2)27C1, STEP, SR3-5, MARK, cis-(+)-Tetrahydro-2-oxothieno[3, Powers, i2pp2a, Proteomes, KI-RAS, 4-d]imidazol-4-yl)pentanoic acid, d230, Cysteine Hydrochloride, Professional Power, P3(40), Reagent, Biotine, Kras2, NS3, Gene, dTAFII250, Development, Medication, broad, Vitamin H, EfW1, PHAPII, cytohesin/GRP1, Investigative, polypeptide chain, dmTAF1, dPAR-1, Taf230, APP-C57, APP-C59, 4beta, Drug Target Prediction, dPar-1, 6aalpha))-, Reagents and Indicators, KRAS2, KRAS1, TAF250, p21B, study, Taf200, reactivo, Coenzyme R, l(2)k06323, ipp2a2, inhibiteur, Medication Development, l(2)SH2 0323, Taf1p, Indicators, inhibidor, Neural-specific protein-tyrosine phosphatase, L Tyrosine, taf-ibeta, (+)-cis-Hexahydro-2-oxo-1H-thieno[3, site, TAF, 9030008G12Rik, par1, TAF[[II]]250, E030013M08Rik, protein complex, igaad, dPAR1, total expressed protein, dPar1, inhibitor, l(3)84Ab, Biotin Gelfert, K-ras, 5-(2-oxohexahydro-1H-thieno[3, 4]imidazole-4-valeric acid, group, Gamma-CTF(50), APP-C99, cis-Tetrahydro-2-oxothieno(3, 4]imidazoline-4-valeric acid, biotin, natural protein, p230, Adap, anon-WO0210402.19, Protein, I2PP2A, TFIID, Professional, AI929937, l(2)SH0323, Zystein, Biodermatin, antagonists, CYH1, Biotin-Ratiopharm, P3(42), PN-II, TAF[[II]]230, 2-amino-3-sulfanylpropanoic acid, hexahydro-2-oxo-, L-2-Amino-3-mercaptopropionic acid, Soluble APP-beta, TAF[II]250, Drug, Protein Gene Products, Computational Prediction of Drug-Target Interactions, dSET/TAF-Ibeta, Personal Power, 2610030F17Rik, DmelCG17603, kras, CFC2, Drug Target, Soluble APP-alpha, PAR1, Par1, assay, Summary, AA407739, 6-diaminohexanoic acid, CVAP, Field Report, TAF1"],"citation_count":["0"],"additional_accession":["PXD022877"]},"is_claimable":false,"name":"Ma et al. 2020 Multiplexed, activity based proteome-wide functional residue profiling","description":"Raw mass spectrometric data files associated with manuscript by Ma et al.","dates":{"publication":"Wed Dec 02 16:13:00 GMT 2020"},"accession":"MSV000086546","cross_references":{"pubmed":["37285454"]}}