1、1,细胞信号转导,2,3,磷酸化共价修饰代谢途径中的关键酶 糖原合成酶：抑制糖原合成 糖原磷酸化酶b激酶 糖原磷酸化酶a ：促进糖原分解 特点：一 被磷酸化共价修饰的蛋白发生生物效应的空间位 置位于胞浆。 二 调节速度相对快。,4,5,cell membrane,Gs/i,cAMP,PKAc,P,1,AC,R,下丘脑的释放激素,ATP,TGACGTCA,gene,CREB,P,CREB,RNA,肾上腺素,胰高血糖素,垂体促激素,抗利尿激素,绒毛膜促性腺激素,甲状旁腺素,大多数肽类激素,AMP,PDE,+,_,茶碱,胰岛素Ca2+CaM,儿茶酚胺，2受体，Gi,儿茶酚胺，受体,生长抑素，2受体，
2、Gi,cell in,cell out,TPK,R,信息物质-X,，,信息物质-X,信息物质-Y,信息物质-Y ？,生长因子,癌蛋白,细胞因子,cAMP介导的信息跨膜传递,生化效应：靶蛋白丝/苏氨酸的磷酸化 抑制糖原合成，促进糖原分解 促进脂肪分解，抑制脂肪酸合成 去除对相关基因转录的阻遏，并同时加速转录与翻译过程 使心肌肌原蛋白易于结合Ca2+，加速心肌肌浆网膜蛋白摄Ca2+ 改变微管蛋白的构象与功能，影响细胞分泌 影响细胞膜蛋白的构象，改变膜对水和离子的通透性,胰岛素，Gi,抗血管紧张素，Gi,促肾上腺皮质激素,Mg2+,ATP,6,7,8,9,10,11,Src Homology dom
3、ain, SH1, SH2 and SH3,SH1: Tyrosine kinase domainSH2: recognizes and binds with high affinity to peptide motifs containing a phosphotyrosine (pTyr) and involves Signal transduction.SH3: binds to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a r
4、ole in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of,12,For examples,SH3,SH3,SH3,SH3,SH3,SH2,SH2,SH2,SH2,SH2,SH2,SH1, tyrosine kinase,Phospholipase C,Phospholipase C,GTPase activating protein,Src,Grb2,GAP,PLC 1,13,1 ME AIAKY*DF*KATADDE*LS1FKRGDILK
5、VLNEECDQN 36 W*YKAELNGKDGFIP1*KNY*IE MKP2H P3WFFGKIP4RAKA 71 EEMLS2KQRHDGAFLIRES3ES4AP5GDFS5LS6VKFGNDV106 QHFKVLRDGAGKYFLWVVKFNS7LNELVDYHRS8TS9VS10R143 NQQIFLR DIEQVP6QQP7T YVQALF*DF*DP8QEDGE*LGFRRG181 DFIHVMDNS11DP9NW*WKGACHGQTGMFP10*RNY*VTP11 VNRNV,Primary structure of Grb2 protein,SH3-3,SH3-2,SH2
6、+7,3-54,59-149,160-212,+2,* proline-rich ligand binding site,14,ME A3IAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIE54 MKP57H P59WFFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFLWVVKFNSLNELVDYHRSTSVSRNQQIFLR149 DIEQVP155QQP158T Y160VQALFDFDPQEDGELGFRRGDFIHVMDNSDPNWWKGACHGQTGMFPRNYVTP
7、212 VNRNV,15,16,Molecular Weight: 529.481 g/molMolecular Formula: C21H32N5O9PHydrogen Bond Donor Count: 7Hydrogen Bond Acceptor Count: 9Rotatable Bond Count: 14 , Charge: 0 Tautomer Count: 32, Heavy Atom Count: 36 Topological Polar Surface Area: 240XLogP: -3.3, Exact Mass: 529.194MonoIsotopic Mass:
8、529.194Complexity: 855, Isotope Atom Count: 0Defined Atom StereoCenter Count: 3Undefined Atom StereoCenter Count: 0Defined Bond StereoCenter Count: 0Undefined Bond StereoCenter Count: 0Covalently-Bonded Unit Count: 1,IUPAC Name: 4-(2R)-2-(2S)-1-(2S)-1,4-diamino-1,4-dioxobutan-2-ylamino-3-methyl-1-ox
9、obutan-2-ylcarbamoyl-4-methylamino-4-oxobutylphenyl dihydrogen phosphateCanonical SMILES: CC(C)C(C(=O)NC(CC(=O)N)C(=O)N)NC(=O)C(CC1=CC=C(C=C1)OP(=O)(O)O)CC(=O)NCIsomeric SMILES: C(C)CH(C(=O)NCH(CC(=O)N)C(=O)N)NC(=O)CH(CC1=CC=C(C=C1)OP(=O)(O)O)CC(=O)NCInChI: InChI=1/C21H32N5O9P/c1-11(2)18(21(31)25-15
10、(19(23)29)10-16(22)27)26-20(30)13(9-17(28)24-3)8-12-4-6-14(7-5-12)35-36(32,33)34/h4-7,11,13,15,18H,8-10H2,1-3H3,(H2,22,27)(H2,23,29)(H,24,28)(H,25,31)(H,26,30)(H2,32,33,34)/t13-,15+,18+/m1/s1/f/h24-26,32-33H,22-23H2,17,Molecular Weight: 46.0254 g/molMolecular Formula: CH2O2Hydrogen Bond Donor Count:
11、 1Hydrogen Bond Acceptor Count: 2Rotatable Bond Count: 0Topological Polar Surface Area: 37.3XLogP: -0.3Exact Mass: 46.0055MonoIsotopic Mass: 46.0055Heavy Atom Count: 3Charge: 0Complexity: 10.3Isotope Atom Count: 0Defined Atom StereoCenter Count: 0Undefined Atom StereoCenter Count: 0Defined Bond Ster
12、eoCenter Count: 0Undefined Bond StereoCenter Count: 0Covalently-Bonded Unit Count: 1IUPAC Name: formic acidCanonical SMILES: C(=O)OInChI: InChI=1/CH2O2/c2-1-3/h1H,(H,2,3)/f/h2H,18,19,Grb2 binds glycerol,glycerol,20,SH3 of Grb2,21,Grb2, N-Terminal Sh3 DomainComplexed With Sos-A Peptide (Nmr, 29 Struc
13、tures),Sos-A: SPLLPKLPPKTYKRE(Mouse )(Homo sapiens, Sos-A : SPHLPKLPPKTYKRE),SH3: GSRRASVG SMEAIAKYDFKATA D DELSFKR G DILKVL NEECDQ NWYKAELNGKDFIPK N YIEMKP HPEFIVTD,22,Sos-A: SPLLPK6LPPK10TYKRE,SH3:GSRRASVGSMEAIAKYDFKATAD23D24E25*LSFKRGDILKVLNEECD42QNWYKAELNGKDFIPKNYIEMKPHPEFIVTD,- D23D24E25*,+ K6,
14、+ K10,- D42,23,24,25,MQQAPQPYEFFSEENSPKWRGLLVSALRKVQVQVHPTLSANEESLYYIEELIFQLLNKLCMAQPRTVQDVEERVQKTFPHPIDKWAIADAQSAIEKRKRRNPLLLPVDKIHPSLKEVLGYKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADKVLMDMFDQDDIGLVSLCEDEPCSSGELNYYDLVRTEIAEERQYLRELNMIIKVFREAFLSDRKLFKPSVYEKIFSNISDIHELTVKLLGLIEDTVEMTDESSPHPLAGS
15、CFEDLAEEQAFDPYETLSQDILSPEFHEHFNKLMARPAVALHFQSIADGFKEAVRYVLPRLMLVPVYHCWHYFELLKQLKACSEEQEDRECLNQAITALMNHQGSMDRIYKQYSPRRRPGDPVCPFYSHQLRSKHLAIKKMNEIQKNIDGWEGKDIGQCCNEFIMEGPLTRIGAKHERHIFLFDGLMISCKPNHGQTRLPGYTSAEYRLKEKFVMRKIQICDKEDTCEHKHAFELVSKDENSIIFAAKSAEEKNNWMAALISLHYRSTLDRMLDSVLLKEENEQPLRLPSPEVYRFVVKD
16、SEENIVFEDNLQSRSGIPIIKGGTVVKLIERLTYHMYADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTDADKLAIEKGEQPISADLKRFRKEYVQPVQLRVLNVFRHWVDHHYYDFERDLELLERLESFISSVRGKAMKKWVESIAKIIRRKKQAQANGVSHNITFESPPPPIEWHISKPGQFETFDLMTLDPIEIARQLTLLESDLYRKVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSRIIEILQVFQDLNNFNGVLEIVSAVNSV
17、SVYRLDHTFEALQERKRKILDEAVELSQDHFKKYLVKLKSINPPCVPFFGIYLTNILKTEEGNNDFLKRKGKDLINFSKRRKVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPMGSASEKEFTDYLFNKSLEIEPRNCKQPPRFPRKSTFSLKSPGIRPNTGRHGSTSGTLRGHPTPLEREPCKISFSRIAETELESTVSAPTSPNTP63STPPVSASSDLSVFLDVDLNSSCGSNSIFAPVLLPHSKSFFSSCGSLHKLSEEPLIPPPLPPRKKFDHDASNSKGNMKSDDDPPAIPP
18、RQPPPPKVKPRVPVPTGAFDGPLHSPPPPPPRDPLPDTPPPVPLRPPEHFINCPFNLQPPPLGHLHRDSDWLRDISTCPNSPSTPPSTPSPRVPRRCYVLSSSQNNLAHPPAPPVPPRQNSSPHLPKLPPKTYKRELSHPPLYRLPLLENAETPQ,SOS2(son of sevenless homolog 2, Homo sapiens)Proline rate: total, 9.3%(124); front part 1088 aa, 5.7%; back part 244 aa, 25.4%,26,Inosital trip
19、hosphate,Diacylglycerol,27,28,MADEEAEQERLSCGEGGCVAELQRLGERLQELELQLRESRVPAVEAATDYCQQLCQTLLEYAEKWKTSEDPLPLLEVYTVAIQSYVKARPYLTSECENVALVLERLALSCVELLLCLPVELSDKQWEQFQTLVQVAHEKLMENGSCELHFLATLAQETGVWKNPVLCTILSQEPLDKDKVNEFLAFEGPILLDMRIKHLIKTNQLSQATALAKLCSDHPEIGIKGSFKQTYLVCLCTSSPNGKLIEEISEVDCKDALEMICNLESEGDEK
20、SALVLCTAFLSRQLQQGDMYCAWELTLFWSKLQQRVEPSIQVYLERCRQLSLLTKTVYHIFFLIKVINSETEGAGLATCIELCVKALRLESTENTEVKISICKTISCLLPDDLEVKRACQLSEFLIEPTVDAYYAVEMLYNQPDQKYDEENLPIPNSLRCELLLVLKTQWPFDPEFWDWKTLKRQCLALMGEEASIVSSIDELNDSEVYEKVVDYQEESKETSMNGLSGGVGANSGLLKDIGDEKQKKREIKQLRERGFISARFRNWQAYMQYCVLCDKEFLGHRIVRHAQKHYKDGIYS
21、CPICAKNFNSKETFVPHVTLHVKQSSKERLAAMKPLRRLGRPPKITTTNENQKTNTVAKQEQRPIKKNSLYSTDFIVFNDNDGSDDENDDKDKSYEPEVIPVQKPVPVNEFNCPVTFCKKGFKYFKNLIAHVKGHKDNEDAKRFLEMQSKKVICQYCRRHFVSVTHLNDHLQMHCGSKPYICIQMKCKAGFNSYAELLTHRKEHQVFRAKCMFPKCGRIFSEAYLLYDHEAQHYNTYTCKFTGCGKVYRSQGELEKHLDDHSTPPEKVLPPEAQLNSSGDSIQPSEVNQNTAENIEKERS
22、MLPSENNIENSLLADRSDAWDKSKAESAVTKQDQISASELRQANGPLSNGLENPATTPLLQSSEVAVSIKVSLNQGIEDNFGKQENSTVEGSGEALVTDLHTPVEDTCNDLCHPGFQERKEQDCFNDAHVTQNSLVNSETLKIGDLTPQNLERQVNNLMTFSVQNQAAFQNNLPTSKFECGDNVKTSSNLYNLPLKTLESIAFVPPQSDLSNSLGTPSVPPKAPVQKFSCQVEGCTRTYNSSQSIGKHMKTAHPDQYAAFKMQRKSKKGQKANNLNTPNNGKFVYFLPSPVNSSNPFFTS
23、QTKANGNPACSAQLQHVSPPIFPAHLASVSTPLLSSMESVINPNITSQDKNEQGGMLCSQMENLPSTALPAQMEDLTKTVLPLNIDSGSDPFLPLPAESSSMSLFPSPADSGTNSVFSQLENNTNHYSSQIEGNTNSSFLKGGNGENAVFPSQVNVANNFSSTNAQQSAPEKVKKDRGRGPNGKERKPKHNKRAKWPAIIRDGKFICSRCYRAFTNPRSLGGHLSKRSYCKPLDGAEIAQELLQSNGQPSLLASMILSTNAVNLQQPQQSTFNPEACFKDPSFLQLLAENRSPAFLPNTF
24、PRSGVTNFNTSVSQEGSEIIKQALETAGIPSTFEGAEMLSHVSTGCVSDASQVNATVMPNPTVPPLLHTVCHPNTLLTNQNRTSNSKTSSIEECSSLPVFPTNDLLLKTVENGLCSSSFPNSGGPSQNFTSNSSRVSVISGPQNTRSSHLNKKGNSASKRRKKVAPPLIAPNASQNLVTSDLTTMGLIAKSVEIPTTNLHSNVIPTCEPQSLVENLTQKLNNVNNQLFMTDVKENFKTSLESHTVLAPLTLKTENGDSQMMALNSCTTSINSDLQISEDNVIQNFEKTLEIIKTAMNSQI
25、LEVKSGSQGAGETSQNAQINYNIQLPSVNTVQNNKLPDSSPFSSFISVMPTKSNIPQSEVSHKEDQIQEILEGLQKLKLENDLSTPASQCVLINTSVTLTPTPVKSTADITVIQPVSEMINIQFNDKVNKPFVCQNQGCNYSAMTKDALFKHYGKIHQYTPEMILEIKKNQLKFAPFKCVVPTCTKTFTRNSNLRAHCQLVHHFTTEEMVKLKIKRPYGRKSQSENVPASRSTQVKKQLAMTEENKKESQPALELRAETQNTHSNVAVIPEKQLVEKKSPDKTESSLQVITVTSEQCNTN
26、ALTNTQTKGRKIRRHKKEKEEKKRKKPVSQSLEFPTRYSPYRPYRC*VHQGC*FAAFTIQQNLILH*YQAVH*KSDLPAFSAEVEEESEAGKESEETETKQTLKEFRCQVSDCSRIFQAITGLIQHYMKLHEMTPEEIESMTASVDVGKFPCDQLECKSSFTTYLNYVVHLEADHGIGLRASKTEEDGVYKCDCEGCDRIYATRSNLLRHIFNKHNDKHKAHLIRPRRLTPGQENMSSKANQEKSKSKHRGTKHSRCGKEGIKMPKTKRKKKNNLENKNAKIVQIEENKPYSLKRGKHVY
27、SIKARNDALSECTSRFVTQYPCMIKGCTSVVTSESNIIRHYKCHKLSKAFTSQHRNLLIVFKRCCNSQVKETSEQEGAKNDVKDSDTCVSESNDNSRTTATVSQKEVEKNEKDEMDELTELFITKLINEDSTSVETQANTSSNVSNDFQEDNLCQSERQKASNLKRVNKEKNVSQNKKRKVEKAEPASAAELSSVRKEEETAVAIQTIEEHPASFDWSSFKPMGFEVSFLKFLEESAVKQKKNTDKDHPNTGNKKGSHSNSRKNIDKTAVTSGNHVCPCKESETFVQFANPSQLQCSDNVKIVLDKNLKDCTELVLKQLQEMKPTVSLKKLEVHSNDPDMSVMKDISIGKATGRGQY,Zinc finger protein 292: 2723 aa, 305KD, pI 7.27, 67+,1,2,3,4,29,
