title: Deciphering enzyme function using peptide arrays.
abstract: Enzymes are key molecules in signal-transduction pathways. However, only a small fraction of more than 500 human kinases, 300 human proteases and 200 human phosphatases is characterised so far. Peptide microarray based technologies for extremely efficient profiling of enzyme substrate specificity emerged in the last years. This technology reduces set-up time for HTS assays and allows the identification of downstream targets. Moreover, peptide microarrays enable optimisation of enzyme substrates. Focus of this review is on assay principles for measuring activities of kinases, phosphatases or proteases and on substrate identification/optimisation for kinases. Additionally, several examples for reliable identification of substrates for lysine methyl-transferases, histone deacetylases and SUMO-transferases are given. Finally, use of high-density peptide microarrays for the simultaneous profiling of kinase activities in complex biological samples like cell lysates or lysates of complete organisms is described. All published examples of peptide arrays used for enzyme profiling are summarised comprehensively.
authors: Institute of Agricultural and Nutritional Sciences, Department of Human Nutrition, Martin-Luther-University Halle-Wittenberg, Von Danckelmann Platz 2, 06120 Halle, Germany.
authors: Alexandra
authors: A
authors: Thiele
authors: Gabriele I
authors: GI
authors: Stangl
authors: Mike
authors: M
authors: Schutkowski
references: Biochemistry. 2008 Jun 10;47(23):6242-50
references: 18470998
references: FASEB J. 2009 Apr;23(4):1127-37
references: 19056838
references: Biochemistry. 1995 Aug 22;34(33):10569-77
references: 7654713
references: J Mol Biol. 2004 Feb 13;336(2):307-11
references: 14757045
references: Science. 2000 Sep 8;289(5485):1760-3
references: 10976071
references: Endocrinology. 2006 Jul;147(7):3555-62
references: 16574792
references: J Fluor Chem. 2009 Nov 1;130(11):1042-1048
references: 20161483
references: Science. 1991 Feb 15;251(4995):767-73
references: 1990438
references: Cancer Res. 2008 Feb 15;68(4):1213-20
references: 18281498
references: Chembiochem. 2010 Jan 25;11(2):235-47
references: 20043307
references: J Am Chem Soc. 2002 Dec 4;124(48):14397-402
references: 12452714
references: Chembiochem. 2009 Mar 23;10(5):877-88
references: 19243087
references: Methods. 2005 Jan;35(1):64-72
references: 15588987
references: Curr Opin Biotechnol. 2002 Aug;13(4):315-20
references: 12323352
references: J Biol Chem. 2011 Feb 11;286(6):4173-85
references: 21123182
references: J Biotechnol. 1995 Jul 31;41(2-3):259-72
references: 7654352
references: Structure. 2008 Feb;16(2):228-38
references: 18275814
references: J Med Chem. 2006 Apr 6;49(7):2147-50
references: 16570909
references: Cancer Res. 2009 Jul 15;69(14):5987-95
references: 19567681
references: Biopolymers. 2010;94(6):810-9
references: 20725946
references: Anal Chem. 2008 Feb 1;80(3):643-50
references: 18179244
references: Methods Mol Biol. 2009;570:287-97
references: 19649600
references: Langmuir. 2007 Apr 10;23(8):4494-7
references: 17367174
references: Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11761-5
references: 8524844
references: Mol Cell Proteomics. 2007 Dec;6(12):2088-99
references: 17698882
references: Biomaterials. 2006 Jun;27(18):3505-14
references: 16499964
references: Science. 2007 Dec 21;318(5858):1888
references: 18096799
references: ACS Chem Biol. 2007 May 22;2(5):299-314
references: 17518431
references: Nat Med. 2008 Nov;14(11):1236-46
references: 18931684
references: Angew Chem Int Ed Engl. 2005 Feb 18;44(9):1408-12
references: 15666425
references: Biotechnol Prog. 2002 May-Jun;18(3):641-6
references: 12052085
references: Nucleosides Nucleotides Nucleic Acids. 2007;26(10-12):1353-7
references: 18066782
references: PLoS One. 2010 Dec 08;5(12):e14255
references: 21170386
references: Methods Mol Biol. 2010;669:135-45
references: 20857363
references: Am J Physiol Renal Physiol. 2007 Jul;293(1):F428-37
references: 17429032
references: Mol Cancer Ther. 2009 Jul;8(7):1846-55
references: 19584230
references: Methods Mol Biol. 2007;382:287-312
references: 18220239
references: Anal Chem. 2002 Oct 15;74(20):5161-8
references: 12403566
references: Bioconjug Chem. 2001 Mar-Apr;12(2):229-39
references: 11312684
references: Anal Chem. 2007 Jan 15;79(2):773-7
references: 17222050
references: Analyst. 2006 Oct;131(10):1097-104
references: 17003856
references: Bioorg Med Chem Lett. 2003 Sep 15;13(18):2997-3000
references: 12941320
references: Appl Biochem Biotechnol. 2011 Mar;163(6):803-12
references: 20878261
references: Comb Chem High Throughput Screen. 2008 Jan;11(1):24-35
references: 18220541
references: Bioorg Med Chem Lett. 2002 Aug 19;12(16):2079-83
references: 12127508
references: Proteomics. 2004 Jun;4(6):1695-702
references: 15174138
references: Anal Chim Acta. 2007 Apr 4;588(1):26-33
references: 17386790
references: Chem Commun (Camb). 2008 Aug 28;(32):3723-5
references: 18685756
references: Biopolymers. 2000;55(3):188-206
references: 11074414
references: Proteomics. 2003 Jul;3(7):1244-55
references: 12872225
references: Org Lett. 2003 Apr 17;5(8):1257-60
references: 12688733
references: J Biol Chem. 2003 Apr 25;278(17):15162-7
references: 12551909
references: Anal Biochem. 2008 Apr 1;375(1):147-9
references: 18167303
references: J Biol Chem. 2009 Aug 14;284(33):22048-22058
references: 19494114
references: Mol Cancer Ther. 2004 Nov;3(11):1439-50
references: 15542783
references: Cancer Res. 2009 Aug 1;69(15):6216-22
references: 19602594
references: Anal Chem. 2005 Jul 1;77(13):3979-85
references: 15987100
references: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6459-64
references: 20308550
references: Clin Exp Metastasis. 2009;26(5):485-96
references: 19294521
references: Anal Biochem. 2004 Jul 15;330(2):311-6
references: 15203338
references: J Cell Biochem. 2010 Apr 1;109(5):957-66
references: 20127719
references: Methods Mol Biol. 2009;570:309-16
references: 19649602
references: Oncogene. 2009 Dec 3;28(48):4249-60
references: 19749798
references: Bioorg Med Chem. 2008 Aug 15;16(16):7788-94
references: 18656369
references: Methods Mol Biol. 1998;87:99-106
references: 9523264
references: J Pept Sci. 2007 Oct;13(10):625-33
references: 17694567
references: Nat Protoc. 2007;2(6):1333-49
references: 17545971
references: Biochem J. 1997 Mar 1;322 ( Pt 2):455-60
references: 9065763
references: Angew Chem Int Ed Engl. 2010 Feb 8;49(7):1252-7
references: 20069617
references: PLoS One. 2007 Aug 22;2(8):e777
references: 17712425
references: J Biol Chem. 1985 Oct 15;260(23):12492-9
references: 2413024
references: Cancer Biol Ther. 2009 Jul;8(13):1239-48
references: 19411826
references: J Am Chem Soc. 2010 May 12;132(18):6419-24
references: 20408521
references: PLoS One. 2007 Jul 04;2(7):e581
references: 17611617
references: FEBS Lett. 1998 Mar 20;425(1):166-70
references: 9541029
references: Angew Chem Int Ed Engl. 2003;42(47):5830-4
references: 14673911
references: Nat Methods. 2007 Jun;4(6):511-6
references: 17486086
references: Anal Chem. 2005 Dec 15;77(24):8013-9
references: 16351150
references: J Biol Chem. 2010 Nov 26;285(48):37762-72
references: 20851891
references: Anal Chem. 2005 Sep 1;77(17):5770-4
references: 16131095
references: Nat Biotechnol. 2002 Sep;20(9):922-6
references: 12134169
references: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7521-6
references: 20368441
references: J Proteome Res. 2010 Oct 1;9(10):5250-61
references: 20726594
references: Mol Cell. 2007 Mar 9;25(5):689-702
references: 17349956
references: Glycoconj J. 2010 Aug;27(6):571-82
references: 20721622
references: Langmuir. 2005 Feb 15;21(4):1489-96
references: 15697299
references: Eur J Biochem. 1998 Jun 1;254(2):433-8
references: 9660202
references: J Biol Chem. 1977 Jul 25;252(14):4888-94
references: 194899
references: Chem Commun (Camb). 2009 Feb 14;(6):677-9
references: 19322419
references: Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):280-8
references: 21088252
references: Biosens Bioelectron. 2010 Oct 15;26(2):424-31
references: 20729058
references: BMC Biochem. 2005 Oct 21;6:22
references: 16242037
references: J Biol Chem. 2004 Nov 19;279(47):49206-13
references: 15355981
references: Methods Mol Biol. 1998;87:25-39
references: 9523256
references: Biochem Biophys Res Commun. 1995 Sep 25;214(3):888-94
references: 7575560
references: J Immunol Methods. 2002 Sep 1;267(1):13-26
references: 12135797
references: Chem Biol. 2004 Oct;11(10):1351-60
references: 15489162
references: EMBO J. 2006 Oct 4;25(19):4686-96
references: 16977320
references: FEBS Lett. 2007 Jan 9;581(1):77-83
references: 17174311
references: Angew Chem Int Ed Engl. 2004 May 10;43(20):2671-4
references: 18629986
references: J Comb Chem. 2000 Jul-Aug;2(4):349-54
references: 10891102
references: Biol Chem. 2002 Jun;383(6):1011-20
references: 12222675
references: Langmuir. 2006 Aug 1;22(16):7059-65
references: 16863260
references: ACS Chem Biol. 2011 Feb 18;6(2):146-57
references: 20945913
references: Cancer Res. 2005 Sep 1;65(17):7699-706
references: 16140937
references: Chem Commun (Camb). 2006 Oct 14;(38):3984-6
references: 17003873
references: Comb Chem High Throughput Screen. 2006 Jan;9(1):21-5
references: 16454683
references: Chem Commun (Camb). 2007 Dec 21;(47):5019-21
references: 18049739
references: Mol Cell. 2011 Jan 21;41(2):139-49
references: 21255725
references: FEBS J. 2008 May;275(10):2561-73
references: 18422655
references: J Biol Chem. 2004 Nov 26;279(48):49571-4
references: 15465828
references: Mol Cell Proteomics. 2011 Mar;10(3):M110.000786
references: 21062935
references: Chembiochem. 2007 May 25;8(8):933-42
references: 17471478
references: J Biol Chem. 2005 Mar 25;280(12):11869-75
references: 15659405
references: Nat Methods. 2004 Oct;1(1):27-9
references: 15782149
references: J Am Chem Soc. 2002 Dec 18;124(50):14868-70
references: 12475327
references: Biol Chem. 2006 Mar;387(3):337-46
references: 16542157
references: Nat Chem. 2010 Feb;2(2):138-45
references: 21124405
references: Biochemistry. 2001 Feb 13;40(6):1694-701
references: 11327829
references: Anal Sci. 2007 Mar;23(3):271-5
references: 17372367
references: Methods Mol Biol. 2010;669:183-94
references: 20857367
references: EMBO Rep. 2002 Mar;3(3):268-73
references: 11850402
references: Nucleic Acids Res. 1999 Jan 1;27(1):237-9
references: 9847189
references: Nat Genet. 2000 Nov;26(3):283-9
references: 11062466
references: J Biol Chem. 2000 Jan 28;275(4):2431-8
references: 10644696
references: Curr Opin Biotechnol. 2001 Feb;12(1):59-64
references: 11167074
references: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14772-7
references: 11121077
references: J Biol Chem. 2009 May 22;284(21):14068-78
references: 19332543
references: J Am Chem Soc. 2007 Jan 10;129(1):10-1
references: 17199263
references: Biosens Bioelectron. 2008 Dec 1;24(4):618-25
references: 18644709
references: Br J Haematol. 2009 Jan;144(1):127-30
references: 19016738
references: Nucleic Acids Res. 2003 Jan 1;31(1):365-70
references: 12520024
references: J Pept Res. 1999 Oct;54(4):319-27
references: 10532237
references: Methods Mol Biol. 1996;66:149-69
references: 8959713
references: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14244-9
references: 11724963
references: J Biol Chem. 2010 Sep 24;285(39):29770-9
references: 20639203
references: Plant Physiol. 2007 Jul;144(3):1481-94
references: 17478632
references: Sci Signal. 2009 Apr 28;2(68):ra19
references: 19401593
references: Int J Radiat Oncol Biol Phys. 2010 Oct 1;78(2):555-62
references: 20675069
references: Pharmacol Ther. 1999 May-Jun;82(2-3):373-87
references: 10454213
references: Nat Chem Biol. 2008 Jun;4(6):344-6
references: 18438403
references: J Biol Chem. 2002 Aug 2;277(31):27839-49
references: 12023960
references: Chem Soc Rev. 2008 Jul;37(7):1330-6
references: 18568159
references: PLoS One. 2010 Feb 04;5(2):e9057
references: 20140229
references: J Biol Chem. 2011 Feb 18;286(7):5494-505
references: 21127067
references: J Proteome Res. 2010 Dec 3;9(12):6467-78
references: 20949974
references: Chembiochem. 2007 Feb 12;8(3):315-22
references: 17226879
references: Blood. 2009 Jan 15;113(3):594-603
references: 18840711
references: J Biol Chem. 2004 Mar 5;279(10):8802-7
references: 14679191
references: Leukemia. 2008 Dec;22(12):2208-16
references: 18784740
references: Anal Biochem. 2008 Apr 15;375(2):223-31
references: 18191030
references: Bioorg Med Chem Lett. 2002 Aug 19;12(16):2085-8
references: 12127509
references: Blood. 2005 Sep 1;106(5):1703-10
references: 15899916
references: Methods Mol Biol. 2009;570:203-19
references: 19649595
references: Nat Mater. 2004 Jan;3(1):58-64
references: 14661016
references: J Biol Chem. 2009 Jun 12;284(24):16170-16182
references: 19372219
references: ACS Chem Biol. 2010 Sep 17;5(9):863-73
references: 20849068
references: PLoS One. 2009 Aug 12;4(8):e6605
references: 19672308
references: Methods Mol Biol. 2010;669:125-33
references: 20857362
references: Mol Cell Proteomics. 2006 Nov;5(11):2124-30
references: 16887929
references: Science. 1994 Nov 4;266(5186):776-9
references: 7973629
references: Bioconjug Chem. 2002 Jul-Aug;13(4):713-20
references: 12121125
references: Angew Chem Int Ed Engl. 2007;46(40):7700-3
references: 17726672
references: J Biochem. 2008 Jul;144(1):39-49
references: 18344540
references: Mol Immunol. 1993 Apr;30(6):577-85
references: 7683750
references: Chem Commun (Camb). 2008 Jan 28;(4):502-4
references: 18188482
references: Methods Mol Biol. 2004;264:191-204
references: 15020791
references: Biochemistry. 2010 Oct 5;49(39):8626-35
references: 20806779
references: Bioconjug Chem. 2001 Mar-Apr;12(2):240-50
references: 11312685
references: Science. 1999 Feb 26;283(5406):1325-8
references: 10037602
references: Nat Biotechnol. 2002 Mar;20(3):270-4
references: 11875428
references: Plant Methods. 2007 Feb 12;3:3
references: 17295910
references: Adv Exp Med Biol. 1997;419:87-91
references: 9193640
references: Plant J. 2008 Jul;55(1):104-17
references: 18363786
references: Mol Microbiol. 2003 Mar;47(5):1317-28
references: 12603737
references: FEBS J. 2009 Dec;276(23):7159-76
references: 19895577
references: Leuk Lymphoma. 2011 Jan;52(1):122-30
references: 21133721
references: Plast Reconstr Surg. 2009 Feb;123(2 Suppl):83S-93S
references: 19182667
references: Chembiochem. 2009 Sep 4;10(13):2159-61
references: 19688789
references: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11139-44
references: 12167675
references: Chem Biol. 2008 Jan;15(1):5-11
references: 18215768
references: Angew Chem Int Ed Engl. 2004 Nov 12;43(44):5973-7
references: 15547909
references: Mol Endocrinol. 2003 Nov;17(11):2228-39
references: 12907755
references: Methods Mol Biol. 2007;381:299-312
references: 17984526
references: Methods Mol Biol. 2009;524:169-80
references: 19377944
references: J Virol. 2007 Feb;81(4):1923-33
references: 17151108
references: Methods Mol Biol. 2010;669:173-81
references: 20857366
references: Mol Divers. 2004;8(3):291-9
references: 15384422
references: Pharmacol Ther. 2002 Feb-Mar;93(2-3):203-15
references: 12191612
references: ACS Chem Biol. 2007 Dec 21;2(12):810-8
references: 18154268
references: Eur J Biochem. 2000 Jan;267(2):337-43
references: 10632703
references: J Bacteriol. 2002 Oct;184(20):5762-71
references: 12270835
references: Arthritis Rheum. 2010 Aug;62(8):2412-23
references: 20506108
references: J Biol Chem. 2005 Feb 18;280(7):5972-82
references: 15572359
references: Biochem J. 2010 Apr 28;428(1):55-65
references: 20196770
references: Curr Opin Chem Biol. 2003 Feb;7(1):55-63
references: 12547427
references: Bioconjug Chem. 2007 Nov-Dec;18(6):1778-85
references: 17953441
references: Mol Biol Cell. 1998 Sep;9(9):2527-43
references: 9725910
references: J Pept Sci. 2009 Jun;15(6):393-7
references: 19308932
references: Angew Chem Int Ed Engl. 2008;47(9):1698-702
references: 18203220
references: Comb Chem High Throughput Screen. 2002 Sep;5(6):429-40
references: 12470273
references: Bioconjug Chem. 2009 Mar 18;20(3):550-7
references: 19222167
references: PLoS One. 2009 Jul 30;4(7):e6440
references: 19649278
references: Comb Chem High Throughput Screen. 2010 Nov;13(9):777-89
references: 20615195
references: Mol Cell Proteomics. 2011 Jan;10(1):M110.004457
references: 20860994
references: Cancer Res. 2006 Dec 15;66(24):11605-12
references: 17178854
references: Protein Sci. 2002 Oct;11(10):2326-34
references: 12237455
references: Anal Biochem. 1994 Feb 1;216(2):431-8
references: 8179201
references: Bioconjug Chem. 2001 May-Jun;12(3):346-53
references: 11353531
references: J Am Chem Soc. 2005 May 25;127(20):7280-1
references: 15898754