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Activity-based proteomics

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The basic unit of ABPP is the probe, which typically consists of two elements: a reactive group (RG, sometimes called a "warhead") and a tag. Additionally, some probes may contain a binding group which enhances selectivity. The reactive group usually contains a specially designed
848: 236:(multidimensional protein identification technology) is especially useful for profiling inhibitor selectivity as the potency of an inhibitor can be tested against hundreds of targets simultaneously. 196:
A major advantage of ABPP is the ability to monitor the availability of the enzyme active site directly, rather than being limited to protein or mRNA abundance. With classes of enzymes such as the
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Abuelyaman AS, Hudig D, Woodard SL, Powers JC (1994). "Fluorescent derivatives of diphenyl phosphonate esters: synthesis and use in the inhibition and cellular localization of serine proteases".
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Kam CM, Abuelyaman AS, Li Z, Hudig D, Powers JC (1993). "Biotinylated isocoumarins, new inhibitors and reagents for detection, localization, and isolation of serine proteases".
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Berger AB, Vitorino PM, Bogyo M (2004). "Activity-based protein profiling: applications to biomarker discovery, in vivo imaging and drug discovery".
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Speers AE, Adam GC, Cravatt BF (April 2003). "Activity-based protein profiling in vivo using a copper(i)-catalyzed azide-alkyne cycloaddition".
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ABPP using probes with different fluorophores in the same lane to simultaneously profile differences in enzyme activities
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superfamily. In this probe the fluorophosphonate is the reactive group (RG) as it binds irreversibly to the active-site
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enabling the identification of hundreds of active enzymes from a single sample. This technique, known as
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technology that uses chemical probes that react with mechanistically related classes of enzymes.
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will not react with an activity-based probe. The tag may be either a reporter such as a
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Proceedings of the National Academy of Sciences of the United States of America
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Proceedings of the National Academy of Sciences of the United States of America
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Matrix-assisted laser desorption ionization-time of flight mass spectrometer
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that often interact with endogenous inhibitors or that exist as inactive
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Saghatelian A, Jessani N, Joseph A, Humphrey M, Cravatt BF (July 2004).
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ABPP were first reported in the 1990s in the study of proteases.
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may be too technical for most readers to understand
365:Liu Y, Patricelli MP, Cravatt BF (December 1999). 212:Multidimensional protein identification technology 564: 8: 228:In recent years ABPP has been combined with 844:Matrix-assisted laser desorption ionization 912: 571: 557: 549: 459: 449: 400: 390: 62:Learn how and when to remove this message 46:, without removing the technical details. 332:Journal of the American Chemical Society 279: 16:Analytical technique to study proteins 886:European Molecular Biology Laboratory 44:make it understandable to non-experts 7: 289:American Journal of Pharmacogenomics 14: 182:Huisgen 1,3-dipolar cycloaddition 924: 923: 911: 301:10.2165/00129785-200404060-00004 117:activity-based protein profiling 23: 864:Chromosome conformation capture 1: 892:National Institutes of Health 168:or an affinity label such as 162:post-translationally modified 808:Structure-based drug design 983: 907: 898:Wellcome Sanger Institute 113:Activity-based proteomics 854:Microfluidic-based tools 699:Human Connectome Project 631:Human Microbiome Project 392:10.1073/pnas.96.26.14694 230:tandem mass spectrometry 839:Electrospray ionization 711:Human Epigenome Project 451:10.1073/pnas.0402784101 104:, a fluorophore for in- 880:DNA Data Bank of Japan 796:Human proteome project 599:Computational genomics 520:Bioconjugate Chemistry 485:Bioconjugate Chemistry 225: 156:. An enzyme that is 109: 859:Isotope affinity tags 813:Expression proteomics 219: 77: 619:Human Genome Project 604:Comparative genomics 829:2-D electrophoresis 803:Call-map proteomics 661:Structural genomics 648:Population genomics 609:Functional genomics 532:10.1021/bc00029a004 497:10.1021/bc00024a021 442:2004PNAS..10110000S 383:1999PNAS...9614694L 258:Related inhibitors 783:Structural biology 594:Cognitive genomics 226: 123:) is a functional 110: 967:Mass spectrometry 939: 938: 834:Mass spectrometer 643:Personal genomics 344:10.1021/ja034490h 249:Mass spectrometry 198:serine hydrolases 180:for use with the 98:serine hydrolases 79:Fluorophosphonate 72: 71: 64: 974: 927: 926: 915: 914: 758:Pharmacogenomics 753:Pharmacogenetics 573: 566: 559: 550: 544: 543: 515: 509: 508: 480: 474: 473: 463: 453: 421: 415: 414: 404: 394: 362: 356: 355: 327: 321: 320: 284: 202:metalloproteases 87:serine hydrolase 67: 60: 56: 53: 47: 27: 26: 19: 982: 981: 977: 976: 975: 973: 972: 971: 962:Protein methods 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111: 58: 49: 33: 706:Epigenomics 638:Pangenomics 234:ABPP-MudPIT 166:fluorophore 150:active site 131:Description 94:nucleophile 52:August 2014 952:Proteomics 946:Categories 791:Proteomics 728:Lipidomics 723:Immunomics 275:References 254:Proteomics 192:Advantages 142:covalently 718:Glycomics 158:inhibited 125:proteomic 102:rhodamine 83:rhodamine 957:Genomics 930:Category 656:genomics 580:Genomics 470:15220480 411:10611275 352:12696868 317:18637390 309:15651898 243:See also 206:zymogens 679:Biochip 540:7849068 505:8305526 438:Bibcode 379:Bibcode 38:Please 587:Fields 538:  503:  468:  461:454150 458:  409:  399:  350:  315:  307:  174:alkyne 172:or an 170:biotin 154:enzyme 91:serine 894:(USA) 654:Socio 402:24710 313:S2CID 178:azide 115:, or 918:List 900:(UK) 888:(EU) 882:(JP) 536:PMID 501:PMID 466:PMID 407:PMID 348:PMID 305:PMID 264:DIFP 262:and 260:MAFP 200:and 160:or 121:ABPP 528:doi 493:doi 456:PMC 446:doi 434:101 397:PMC 387:doi 340:doi 336:125 297:doi 222:gel 220:In- 188:). 176:or 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Index

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Fluorophosphonate
rhodamine
serine hydrolase
serine
nucleophile
serine hydrolases
rhodamine
gel
proteomic
electrophile
covalently
nucleophilic
active site
enzyme
inhibited
post-translationally modified
fluorophore
biotin
alkyne
azide
Huisgen 1,3-dipolar cycloaddition
click chemistry
serine hydrolases
metalloproteases
zymogens

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