Abstract
Activity-based protein profiling (ABPP) is emerging as a mature method for chemically interrogating the proteome of a cell. This chapter serves to introduce the reader to ABPP by providing overviews of the general principles of the technique, analytical methods used in ABPP, the classes of enzymes that can be specifically addressed by ABPP probes, and biological applications of ABPP.
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Abbreviations
- (TOP)-ABPP:
-
Tandem orthogonal proteolysis ABPP
- 3-oxo-C12-HSL:
-
3-Oxo-dodecanoyl homoserine lactone
- ABPP:
-
Activity-based protein profiling
- ADP:
-
Adenosine diphosphate
- AOMK:
-
Acyloxymethyl ketone
- ASPP:
-
Active site peptide profiling
- ATP:
-
Adenosine triphosphate
- BODIPY:
-
Boron-dipyrromethane
- CE:
-
Capillary electrophoresis
- FDA:
-
Food and Drug Administration
- FP:
-
Fluorophosphonate
- HDAC:
-
Histone deacetylase
- LC-MS:
-
Liquid chromatography–mass spectrometry
- LIF:
-
Laser-induced fluorescence
- ML:
-
Mixed lineage
- MP:
-
Metalloprotease
- MS:
-
Mass spectrometry
- MudPIT:
-
Multidimensional protein identification technology
- PAD4:
-
Protein arginine deiminase 4
- PI3K:
-
Phosphoinositide 3-kinase
- PKMT:
-
Protein lysine methyltransferase
- PNA:
-
Peptide nucleic acid
- RA:
-
Rheumatoid arthritis
- SAHA:
-
Suberoylanilide hydroxamic acid
- SAM:
-
S-Adenosyl-l-methionine
- SDS:
-
Sodium dodecylsulfate
- SDS-PAGE:
-
Sodium dodecylsulfate polyacrylamide gel electrophoresis
- TEV:
-
Tobacco etch virus
References
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70
Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799
Kobe B, Kemp BE (1999) Active site-directed protein regulation. Nature 402:373–376
Walsh CT (2006) Posttranslational modification of proteins: expanding nature’s inventory. Roberts, Englewood, CO
Gygi SP, Rist B, Gerber SA et al (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17:994–999
Washburn MP, Wolters D, Yates JR 3rd (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19:242–247
Zhu H, Bilgin M, Snyder M (2003) Proteomics. Annu Rev Biochem 72:783–812
Ito T, Ota K, Kubota H et al (2002) Roles for the two-hybrid system in exploration of the yeast protein interactome. Mol Cell Proteomics 1:561–566
MacBeath G (2002) Protein microarrays and proteomics. Nat Genet 32(Suppl):526–532
Evans MJ, Cravatt BF (2006) Mechanism-based profiling of enzyme families. Chem Rev 106:3279–3301
Heal WP, Dang TH, Tate EW (2011) Activity-based probes: discovering new biology and new drug targets. Chem Soc Rev 40:246–257
Cravatt BF, Wright AT, Kozarich JW (2008) Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu Rev Biochem 77:383–414
Bottcher T, Pitscheider M, Sieber SA (2010) Natural products and their biological targets: proteomic and metabolomic labeling strategies. Angew Chem Int Ed Engl 49:2680–2698
Barglow KT, Cravatt BF (2007) Activity-based protein profiling for the functional annotation of enzymes. Nat Methods 4:822–827
Dennehy MK, Richards KA, Wernke GR et al (2006) Cytosolic and nuclear protein targets of thiol-reactive electrophiles. Chem Res Toxicol 19:20–29
Scaloni A, Ferranti P, De Simone G et al (1999) Probing the reactivity of nucleophile residues in human 2,3-diphosphoglycerate/deoxy-hemoglobin complex by aspecific chemical modifications. FEBS Lett 452:190–194
Slaughter DE, Hanzlik RP (1991) Identification of epoxide- and quinone-derived bromobenzene adducts to protein sulfur nucleophiles. Chem Res Toxicol 4:349–359
Rando RR (1977) Mechanism-based irreversible enzyme inhibitors. Methods Enzymol 46:28–41
Drahl C, Cravatt BF, Sorensen EJ (2005) Protein-reactive natural products. Angew Chem Int Ed Engl 44:5788–5809
Pitscheider M, Sieber SA (2009) Cinnamic aldehyde derived probes for the active site labeling of pathogenesis associated enzymes. Chem Commun 2009:3741–3743
Weerapana E, Simon GM, Cravatt BF (2008) Disparate proteome reactivity profiles of carbon electrophiles. Nat Chem Biol 4:405–407
Evans MJ, Saghatelian A, Sorensen EJ et al (2005) Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling. Nat Biotechnol 23:1303–1307
Robinette D, Neamati N, Tomer KB et al (2006) Photoaffinity labeling combined with mass spectrometric approaches as a tool for structural proteomics. Expert Rev Proteomics 3:399–408
Tanaka Y, Bond MR, Kohler JJ (2008) Photocrosslinkers illuminate interactions in living cells. Mol Biosyst 4:473–480
Bissantz C, Kuhn B, Stahl M (2010) A medicinal chemist’s guide to molecular interactions. J Med Chem 53:5061–5084
Rostovtsev VV, Green LG, Fokin VV et al (2002) A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed Engl 41:2596–2599
Meldal M, Tornoe CW (2008) Cu-catalyzed azide-alkyne cycloaddition. Chem Rev 108:2952–3015
Speers AE, Adam GC, Cravatt BF (2003) Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3+2] cycloaddition. J Am Chem Soc 125:4686–4687
Saxon E, Bertozzi CR (2000) Cell surface engineering by a modified Staudinger reaction. Science 287:2007–2010
Kohn M, Breinbauer R (2004) The Staudinger ligation-a gift to chemical biology. Angew Chem Int Ed Engl 43:3106–3116
Agard NJ, Prescher JA, Bertozzi CR (2004) A strain-promoted [3+2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc 126:15046–15047
Beatty KE, Fisk JD, Smart BP et al (2010) Live-cell imaging of cellular proteins by a strain-promoted azide-alkyne cycloaddition. Chembiochem 11:2092–2095
Codelli JA, Baskin JM, Agard NJ et al (2008) Second-generation difluorinated cyclooctynes for copper-free click chemistry. J Am Chem Soc 130:11486–11493
Amara N, Mashiach R, Amar D et al (2009) Covalent inhibition of bacterial quorum sensing. J Am Chem Soc 131:10610–10619
Liu S, Zhou B, Yang H et al (2008) Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases. J Am Chem Soc 130:8251–8260
Adam GC, Sorensen EJ, Cravatt BF (2002) Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype. Nat Biotechnol 20:805–809
Patricelli MP, Giang DK, Stamp LM et al (2001) Direct visualization of serine hydrolase activities in complex proteomes using fluorescent active site-directed probes. Proteomics 1:1067–1071
Liu Y, Patricelli MP, Cravatt BF (1999) Activity-based protein profiling: the serine hydrolases. Proc Natl Acad Sci USA 96:14694–14699
Kidd D, Liu Y, Cravatt BF (2001) Profiling serine hydrolase activities in complex proteomes. Biochemistry 40:4005–4015
Santoni V, Molloy M, Rabilloud T (2000) Membrane proteins and proteomics: un amour impossible? Electrophoresis 21:1054–1070
Corthals GL, Wasinger VC, Hochstrasser DF et al (2000) The dynamic range of protein expression: a challenge for proteomic research. Electrophoresis 21:1104–1115
Bottcher T, Sieber SA (2010) Showdomycin as a versatile chemical tool for the detection of pathogenesis-associated enzymes in bacteria. J Am Chem Soc 132:6964–6972
Tully SE, Cravatt BF (2010) Activity-based probes that target functional subclasses of phospholipases in proteomes. J Am Chem Soc 132:3264–3265
Jessani N, Niessen S, Wei BQ et al (2005) A streamlined platform for high-content functional proteomics of primary human specimens. Nat Methods 2:691–697
Liu H, Sadygov RG, Yates JR 3rd (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76:4193–4201
Old WM, Meyer-Arendt K, Aveline-Wolf L et al (2005) Comparison of label-free methods for quantifying human proteins by shotgun proteomics. Mol Cell Proteomics 4:1487–1502
Adam GC, Burbaum J, Kozarich JW et al (2004) Mapping enzyme active sites in complex proteomes. J Am Chem Soc 126:1363–1368
Okerberg ES, Wu J, Zhang B et al (2005) High-resolution functional proteomics by active-site peptide profiling. Proc Natl Acad Sci USA 102:4996–5001
Speers AE, Cravatt BF (2005) A tandem orthogonal proteolysis strategy for high-content chemical proteomics. J Am Chem Soc 127:10018–10019
Sieber SA, Mondala TS, Head SR et al (2004) Microarray platform for profiling enzyme activities in complex proteomes. J Am Chem Soc 126:15640–15641
Kodadek T (2001) Protein microarrays: prospects and problems. Chem Biol 8:105–115
Winssinger N, Ficarro S, Schultz PG et al (2002) Profiling protein function with small molecule microarrays. Proc Natl Acad Sci USA 99:11139–11144
Clark JD, Schievella AR, Nalefski EA et al (1995) Cytosolic phospholipase A2. J Lipid Mediat Cell Signal 12:83–117
Mignatti P, Rifkin DB (1996) Plasminogen activators and angiogenesis. Curr Top Microbiol Immunol 213(Pt 1):33–50
DeClerck YA, Imren S, Montgomery AM et al (1997) Proteases and protease inhibitors in tumor progression. Adv Exp Med Biol 425:89–97
Gorrell MD (2005) Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin Sci (Lond) 108:277–292
Walsh CT (1979) Enzymatic reaction mechanisms. W.H. Freeman, New York
Powers JC, Asgian JL, Ekici OD et al (2002) Irreversible inhibitors of serine, cysteine, and threonine proteases. Chem Rev 102:4639–4750
Bouma BN, Miles LA, Beretta G et al (1980) Human plasma prekallikrein. Studies of its activation by activated factor XII and of its inactivation by diisopropyl phosphofluoridate. Biochemistry 19:1151–1160
Jessani N, Humphrey M, McDonald WH et al (2004) Carcinoma and stromal enzyme activity profiles associated with breast tumor growth in vivo. Proc Natl Acad Sci USA 101:13756–13761
Jessani N, Liu Y, Humphrey M et al (2002) Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness. Proc Natl Acad Sci USA 99:10335–10340
Mahrus S, Craik CS (2005) Selective chemical functional probes of granzymes A and B reveal granzyme B is a major effector of natural killer cell-mediated lysis of target cells. Chem Biol 12:567–577
Gelb BD, Shi GP, Chapman HA et al (1996) Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science 273:1236–1238
Sloane BF, Yan S, Podgorski I et al (2005) Cathepsin B and tumor proteolysis: contribution of the tumor microenvironment. Semin Cancer Biol 15:149–157
Yan S, Sameni M, Sloane BF (1998) Cathepsin B and human tumor progression. Biol Chem 379:113–123
Shenai BR, Sijwali PS, Singh A et al (2000) Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J Biol Chem 275:29000–29010
Iwata Y, Mort JS, Tateishi H et al (1997) Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthritis. Arthritis Rheum 40:499–509
Barrett AJ, Kembhavi AA, Brown MA et al (1982) L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J 201:189–198
Barrett AJ, Kembhavi AA, Hanada K (1981) E-64 [L-trans-epoxysuccinyl-leucyl-amido(4-guanidino)butane] and related epoxides as inhibitors of cysteine proteinases. Acta Biol Med Ger 40:1513–1517
Palmer JT, Rasnick D, Klaus JL et al (1995) Vinyl sulfones as mechanism-based cysteine protease inhibitors. J Med Chem 38:3193–3196
Shaw E (1994) Peptidyl diazomethanes as inhibitors of cysteine and serine proteinases. Methods Enzymol 244:649–656
Shaw E, Angliker H, Rauber P et al (1986) Peptidyl fluoromethyl ketones as thiol protease inhibitors. Biomed Biochim Acta 45:1397–1403
Pliura DH, Bonaventura BJ, Smith RA et al (1992) Comparative behaviour of calpain and cathepsin B toward peptidyl acyloxymethyl ketones, sulphonium methyl ketones and other potential inhibitors of cysteine proteinases. Biochem J 288(Pt 3):759–762
Fonovic M, Bogyo M (2007) Activity based probes for proteases: applications to biomarker discovery, molecular imaging and drug screening. Curr Pharm Des 13:253–261
Brady KD, Giegel DA, Grinnell C et al (1999) A catalytic mechanism for caspase-1 and for bimodal inhibition of caspase-1 by activated aspartic ketones. Bioorg Med Chem 7:621–631
Dai Y, Hedstrom L, Abeles RH (2000) Inactivation of cysteine proteases by (acyloxy)methyl ketones using S′-P′ interactions. Biochemistry 39:6498–6502
Kato D, Boatright KM, Berger AB et al (2005) Activity-based probes that target diverse cysteine protease families. Nat Chem Biol 1:33–38
Mitic N, Smith SJ, Neves A et al (2006) The catalytic mechanisms of binuclear metallohydrolases. Chem Rev 106:3338–3363
Whittaker M, Floyd CD, Brown P et al (1999) Design and therapeutic application of matrix metalloproteinase inhibitors. Chem Rev 99:2735–2776
Skiles JW, Gonnella NC, Jeng AY (2001) The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr Med Chem 8:425–474
Hooper NM, Turner AJ (2002) The search for alpha-secretase and its potential as a therapeutic approach to Alzheimer s disease. Curr Med Chem 9:1107–1119
Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166
Sierevogel MJ, Pasterkamp G, de Kleijn DP et al (2003) Matrix metalloproteinases: a therapeutic target in cardiovascular disease. Curr Pharm Des 9:1033–1040
Sieber SA, Niessen S, Hoover HS et al (2006) Proteomic profiling of metalloprotease activities with cocktails of active-site probes. Nat Chem Biol 2:274–281
Saghatelian A, Jessani N, Joseph A et al (2004) Activity-based probes for the proteomic profiling of metalloproteases. Proc Natl Acad Sci USA 101:10000–10005
Chan EW, Chattopadhaya S, Panicker RC et al (2004) Developing photoactive affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases. J Am Chem Soc 126:14435–14446
Minucci S, Pelicci PG (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6:38–51
Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784
Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25:84–90
Salisbury CM, Cravatt BF (2007) Activity-based probes for proteomic profiling of histone deacetylase complexes. Proc Natl Acad Sci USA 104:1171–1176
Overkleeft HS et al. (2012) Photoaffinity labeling in activity-based protein profiling. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_XXX
Manning G, Whyte DB, Martinez R et al (2002) The protein kinase complement of the human genome. Science 298:1912–1934
Elphick LM, Lee SE, Gouverneur V et al (2007) Using chemical genetics and ATP analogs to dissect protein kinase function. ACS Chem Biol 2:299–314
Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353:172–187
Wymann MP, Marone R (2005) Phosphoinositide 3-kinase in disease: timing, location, and scaffolding. Curr Opin Cell Biol 17:141–149
Noble ME, Endicott JA, Johnson LN (2004) Protein kinase inhibitors: insights into drug design from structure. Science 303:1800–1805
Fedorov O, Marsden B, Pogacic V et al (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA 104:20523–20528
Fedorov O, Sundstrom M, Marsden B et al (2007) Insights for the development of specific kinase inhibitors by targeted structural genomics. Drug Discov Today 12:365–372
Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9:576–596
Zheng J, Knighton DR, ten Eyck LF et al (1993) Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor. Biochemistry 32:2154–2161
Patricelli MP, Szardenings AK, Liyanage M et al (2007) Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 46:350–358
Arcaro A, Wymann MP (1993) Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. Biochem J 296(Pt 2):297–301
Yano H, Nakanishi S, Kimura K et al (1993) Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J Biol Chem 268:25846–25856
Breinbauer R et al. (2012) Activity Based Protein Profiling for Natural Product Target Discovery. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_XXX
Gupta V, Ogawa AK, Du X et al (1997) A model for binding of structurally diverse natural product inhibitors of protein phosphatases PP1 and PP2A. J Med Chem 40:3199–3206
Zhou L, Yu H, Chen K (2002) Relationship between microcystin in drinking water and colorectal cancer. Biomed Environ Sci 15:166–171
Goldberg J, Huang HB, Kwon YG et al (1995) Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376:745–753
Shreder KR, Liu Y, Nomanhboy T et al (2004) Design and synthesis of AX7574: a microcystin-derived, fluorescent probe for serine/threonine phosphatases. Bioconjug Chem 15:790–798
Lo LC, Pang TL, Kuo CH et al (2002) Design and synthesis of class-selective activity probes for protein tyrosine phosphatases. J Proteome Res 1:35–40
Kumar S, Zhou B, Liang F et al (2004) Activity-based probes for protein tyrosine phosphatases. Proc Natl Acad Sci USA 101:7943–7948
Zechel DL, Withers SG (2000) Glycosidase mechanisms: anatomy of a finely tuned catalyst. Acc Chem Res 33:11–18
Tsai CS, Li YK, Lo LC (2002) Design and synthesis of activity probes for glycosidases. Org Lett 4:3607–3610
Wicki J, Rose DR, Withers SG (2002) Trapping covalent intermediates on beta-glycosidases. Methods Enzymol 354:84–105
Vocadlo DJ, Bertozzi CR (2004) A strategy for functional proteomic analysis of glycosidase activity from cell lysates. Angew Chem Int Ed Engl 43:5338–5342
Vocadlo DJ, Hang HC, Kim EJ et al (2003) A chemical approach for identifying O-GlcNAc-modified proteins in cells. Proc Natl Acad Sci USA 100:9116–9121
Denisov IG, Makris TM, Sligar SG et al (2005) Structure and chemistry of cytochrome P450. Chem Rev 105:2253–2277
Guengerich FP, Wu ZL, Bartleson CJ (2005) Function of human cytochrome P450s: characterization of the orphans. Biochem Biophys Res Commun 338:465–469
Hughes AL, Powell DW, Bard M et al (2007) Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metab 5:143–149
Aguiar M, Masse R, Gibbs BF (2005) Regulation of cytochrome P450 by posttranslational modification. Drug Metab Rev 37:379–404
Wright AT, Cravatt BF (2007) Chemical proteomic probes for profiling cytochrome p450 activities and drug interactions in vivo. Chem Biol 14:1043–1051
Wright AT, Song JD, Cravatt BF (2009) A suite of activity-based probes for human cytochrome P450 enzymes. J Am Chem Soc 131:10692–10700
Jones JE, Causey CP, Knuckley B et al (2009) Protein arginine deiminase 4 (PAD4): current understanding and future therapeutic potential. Curr Opin Drug Discov Devel 12:616–627
Vossenaar ER, van Venrooij WJ (2004) Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res Ther 6:107–111
Luo Y, Arita K, Bhatia M et al (2006) Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. Biochemistry 45:11727–11736
Luo Y, Knuckley B, Lee YH et al (2006) A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. J Am Chem Soc 128:1092–1093
Stone EM, Schaller TH, Bianchi H et al (2005) Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase. Biochemistry 44:13744–13752
Slack JL, Causey CP, Luo Y et al (2011) Development and use of clickable activity based protein profiling agents for protein arginine deiminase 4. ACS Chem Biol 6:466–476
Luo Y, Knuckley B, Bhatia M et al (2006) Activity-based protein profiling reagents for protein arginine deiminase 4 (PAD4): synthesis and in vitro evaluation of a fluorescently labeled probe. J Am Chem Soc 128:14468–14469
Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847
Bogyo M, McMaster JS, Gaczynska M et al (1997) Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc Natl Acad Sci USA 94:6629–6634
Bochtler M, Ditzel L, Groll M et al (1999) The proteasome. Annu Rev Biophys Biomol Struct 28:295–317
Jackson G, Einsele H, Moreau P et al (2005) Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies. Cancer Treat Rev 31:591–602
Richardson PG, Mitsiades C, Hideshima T et al (2006) Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu Rev Med 57:33–47
Meng L, Kwok BH, Sin N et al (1999) Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Res 59:2798–2801
Chauhan D, Catley L, Li G et al (2005) A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 8:407–419
Baumeister W, Walz J, Zuhl F et al (1998) The proteasome: paradigm of a self-compartmentalizing protease. Cell 92:367–380
Verdoes M, Florea BI, Menendez-Benito V et al (2006) A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo. Chem Biol 13:1217–1226
Verdoes M, Willems LI, van der Linden WA et al (2010) A panel of subunit-selective activity-based proteasome probes. Org Biomol Chem 8:2719–2727
Geurink PP, Florea BI, Van der Marel GA et al (2010) Probing the proteasome cavity in three steps: bio-orthogonal photo-reactive suicide substrates. Chem Commun (Camb) 46:9052–9054
Spannhoff A, Sippl W, Jung M (2009) Cancer treatment of the future: inhibitors of histone methyltransferases. Int J Biochem Cell Biol 41:4–11
Ryu H, Lee J, Hagerty SW et al (2006) ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc Natl Acad Sci USA 103:19176–19181
Berdasco M, Ropero S, Setien F et al (2009) Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci USA 106:21830–21835
Kurotaki N, Imaizumi K, Harada N et al (2002) Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 30:365–366
Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705
Smith BC, Denu JM (2009) Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta 1789:45–57
Cole PA (2008) Chemical probes for histone-modifying enzymes. Nat Chem Biol 4:590–597
Chuikov S, Kurash JK, Wilson JR et al (2004) Regulation of p53 activity through lysine methylation. Nature 432:353–360
Huang J, Perez-Burgos L, Placek BJ et al (2006) Repression of p53 activity by Smyd2-mediated methylation. Nature 444:629–632
Subramanian K, Jia D, Kapoor-Vazirani P et al (2008) Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 30:336–347
Lee JS, Kim Y, Kim IS et al (2010) Negative regulation of hypoxic responses via induced Reptin methylation. Mol Cell 39:71–85
Binda O, Boyce M, Rush JS et al (2011) A chemical method for labeling lysine methyltransferase substrates. Chembiochem 12:330–334
Islam K, Zheng W, Yu H et al (2011) Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling. ACS Chem Biol 6(7):679–684
Peters W, Willnow S, Duisken M et al (2010) Enzymatic site-specific functionalization of protein methyltransferase substrates with alkynes for click labeling. Angew Chem Int Ed Engl 49:5170–5173
Krivtsov AV, Armstrong SA (2007) MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 7:823–833
Tachibana M, Sugimoto K, Fukushima T et al (2001) Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 276:25309–25317
Rathert P, Dhayalan A, Murakami M et al (2008) Protein lysine methyltransferase G9a acts on non-histone targets. Nat Chem Biol 4:344–346
Wozniak RJ, Klimecki WT, Lau SS et al (2007) 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene 26:77–90
Wang R, Zheng W, Yu H et al (2011) Labeling substrates of protein arginine methyltransferase with engineered enzymes and matched S-adenosyl-L-methionine analogues. J Am Chem Soc 133:7648–7651
Shah K, Liu Y, Deirmengian C et al (1997) Engineering unnatural nucleotide specificity for Rous sarcoma virus tyrosine kinase to uniquely label its direct substrates. Proc Natl Acad Sci USA 94:3565–3570
Liu Y, Shah K, Yang F et al (1998) Engineering Src family protein kinases with unnatural nucleotide specificity. Chem Biol 5:91–101
Bishop AC, Ubersax JA, Petsch DT et al (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407:395–401
Adam GC, Cravatt BF, Sorensen EJ (2001) Profiling the specific reactivity of the proteome with non-directed activity-based probes. Chem Biol 8:81–95
Barglow KT, Cravatt BF (2004) Discovering disease-associated enzymes by proteome reactivity profiling. Chem Biol 11:1523–1531
Barglow KT, Cravatt BF (2006) Substrate mimicry in an activity-based probe that targets the nitrilase family of enzymes. Angew Chem Int Ed Engl 45:7408–7411
Rhee SG (2006) Cell signaling. H2O2, a necessary evil for cell signaling. Science 312:1882–1883
Terada LS (2006) Specificity in reactive oxidant signaling: think globally, act locally. J Cell Biol 174:615–623
D’Autreaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824
Poole LB, Nelson KJ (2008) Discovering mechanisms of signaling-mediated cysteine oxidation. Curr Opin Chem Biol 12:18–24
Reddie KG, Carroll KS (2008) Expanding the functional diversity of proteins through cysteine oxidation. Curr Opin Chem Biol 12:746–754
Benitez LV, Allison WS (1974) The inactivation of the acyl phosphatase activity catalyzed by the sulfenic acid form of glyceraldehyde 3-phosphate dehydrogenase by dimedone and olefins. J Biol Chem 249:6234–6243
Leonard SE, Garcia FJ, Goodsell DS et al (2011) Redox-based probes for protein tyrosine phosphatases. Angew Chem Int Ed Engl 50:4423–4427
Leonard SE, Reddie KG, Carroll KS (2009) Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. ACS Chem Biol 4:783–799
Jessani N, Young JA, Diaz SL et al (2005) Class assignment of sequence-unrelated members of enzyme superfamilies by activity-based protein profiling. Angew Chem Int Ed Engl 44:2400–2403
Hayes BK, Varki A (1989) O-acetylation and de-O-acetylation of sialic acids. Sialic acid esterases of diverse evolutionary origins have serine active sites and essential arginine residues. J Biol Chem 264:19443–19448
Li YM, Xu M, Lai MT et al (2000) Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405:689–694
Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270
Christofk HR, Vander Heiden MG, Wu N et al (2008) Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452:181–186
Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744
Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777
Mohamed MM, Sloane BF (2006) Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 6:764–775
Ramos-DeSimone N, Hahn-Dantona E, Sipley J et al (1999) Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274:13066–13076
Jessani N, Niessen S, Mueller BM et al (2005) Breast cancer cell lines grown in vivo: what goes in isn’t always the same as what comes out. Cell Cycle 4:253–255
Joyce JA, Baruch A, Chehade K et al (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5:443–453
Taubes G (2008) The bacteria fight back. Science 321:356–361
Heal WP, Tate EW (2012) On the Applications of Activity-Based Protein Profiling to Microbial Pathogenesis. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_299
Blum G, von Degenfeld G, Merchant MJ et al (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol 3:668–677
Jedeszko C, Sloane BF (2004) Cysteine cathepsins in human cancer. Biol Chem 385:1017–1027
Harbeck N, Alt U, Berger U et al (2001) Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy. Clin Cancer Res 7:2757–2764
Foekens JA, Kos J, Peters HA et al (1998) Prognostic significance of cathepsins B and L in primary human breast cancer. J Clin Oncol 16:1013–1021
Rayo J, Amara N, Krief P et al (2011) Live cell labeling of native intracellular bacterial receptors using aniline-catalyzed oxime ligation. J Am Chem Soc 133(19):7469–7475
Krysiak J, Breinbauer R (2012) Activity-based protein profiling for natural product target discovery. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_289
Bulaj G, Kortemme T, Goldenberg DP (1998) Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 37:8965–8972
Lewis CT, Seyer JM, Carlson GM (1989) Cysteine 288: an essential hyperreactive thiol of cytosolic phosphoenolpyruvate carboxykinase (GTP). J Biol Chem 264:27–33
Knowles JR (1976) The intrinsic pKa-values of functional groups in enzymes: improper deductions from the pH-dependence of steady-state parameters. CRC Crit Rev Biochem 4:165–173
Weerapana E, Wang C, Simon GM et al (2010) Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature 468:790–795
Acknowledgments
M. Nodwell thanks the Alexander von Humboldt foundation for a postdoctoral fellowship. S. Sieber is supported by the Deutsche Forschungsgemeinschaft (Emmy Noether), SFB749, FOR1406, an ERC starting grant, and the Center for Integrated Protein Science Munich CIPSM.
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Nodwell, M.B., Sieber, S.A. (2011). ABPP Methodology: Introduction and Overview. In: Sieber, S. (eds) Activity-Based Protein Profiling. Topics in Current Chemistry, vol 324. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_302
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DOI: https://doi.org/10.1007/128_2011_302
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