phase 2 (PDF) - ENDscript

2CHU_A 3ZK3_A 3ZKW_B 3GFV_A 4JCC_A 4MX8_A 3TEF_A 3EIW_A 3TNY_A 3EIX_A 3TLK_A 3HXP_A 3MWF_A

β1 jjjk jjjjk jjjk jjjjjjjjk

β2 β3 β4 α1 η1 β5 η2 η3 α2 β6 η4 α3 β7 α4 α5 jjjjk jjjjk jjk iiiiiiiii llljjk lll llllll iiiiii jjjk llliiiii jjk iiiiiiiiiiiiiiii ii. . iiiiiiiiiii iiiiiiiiiii jjjjjk jjjjjk jjk iiiiiiiii llljjk lll llllll jk jk iiiiiii jjjk llliiiiiii jjk iiiiiiiiiiiiiiii S TT TT jjjjk jjjjk jjk iiiiiiiii llljjk llllll iiiiiii jjjk ll. . . llllliiiii jjk iiiiiiiiiiiiiii ii.. .. iiiiiiiiiii TT jjjjjk jjjjjjjk jjk iiiiiiiii llljjjk lllllll jk iiiiii jjjk llllliiiiiii jjk llliiiiiiiiiiiiiii TT ... . . iiiiiiiiiii jjk T Tjjjjjjjjk jjk iiiiiiiii llljjjk llllllll iiiiii jjk l jk iiiiiiiiiiiiii iiiiiiiiiiiiiiii S S jjk S S S S S S S S S . . . l jk . . . llllliiiiiii jjk iiiiiiiii jjjk lll iiii jj. . . jjjjk iiiiiii jjjk ll. . . llllliiiii jjk iiiiiiiiiiiiiiii iiii TT . . iiiiiiiiiii jjjjjk jjjjjk jjjk iiiiiiiii jk lllllll iiiiii jjjk llllliiiiiii jjk iiiiiiiiiiiiiiii TT TT TT ... TTT . . iiiiiiiii jjjjjk jjk iiiiiiiii jk iiiiii jjjjk iiiiiii jjjk iiiiiiiiiiiiii i S S SS S S SS T T jjjjjkT T T T lll iiiiiii S jk T..T . . iiiiiiiiiii jjjjjk jjk iiiiiiiii jjj lll jjjjkT T jkS iiiiii jjjjkii jjjk iiii iSi. . iiiiiiiiiii SS SS T T jjjjjk ........k TT . . . iillliiiii . . . iiiiiii jjjjjk jjk iiiiiiiii jk iiiiii jjjjk iiiiiii jjjk iiiiiiiiiiiiii S S SSS S S S SS S T T jjjjjkT T T T lll iiiiiii S jk T..T . . iiiiiiiiiii jjj. . . . . . . . jkT T jjjjk jjk iiiiiiiii jjjjjk llliiiii jjjjk iiiii jjjjk llliiiii jjjk iiii TT TT TT ...i TT . . . iiiiiiii i. . iiiiiiiiiii jjk llliiiiiii jjk iiii iiii iiii jjjjk llll jjjk i iiiiiii i iiiiiiiiiii .... .. jjjjk TT TT jjjjk jjk jjjk iiii S iiiiiiiii S jk S lll T T jk jkST T jk iiiiii jjjjkiiT .. .. .. Tiillliiiiiii S S TT . . . iiiiiiii i. . iiiiiiiiiii X X X X X X X X X X X X X X X LPISMSDE.....GDSFLV c A KD..SLG c A ENKI c A PKNP c A SK cc DEEF VV c c I LDLGILD c A TFDAL c A KL c A NDKVV ccc DEF GVP........AKNLPKYLQQFKN...K..PS ccc DEF VGGVQQVDFE c A AI c A NAL c A KP cccc DEEEEF DLII cc IS.G...R c A QSKFYDKL c A KEI cccc DEEEF APTL c FVGLD.NANFLSS c A FENNVLSV c A AK cc DF LYGLE c A ..KEA c A LEKI c A SDIK AcBc LPISMSDE.....GDSFLV c B KD..SLG c B ENKI c B PKNP c B SK cc KddG VV c c I LDLGILD c B TFDAL c B KL c B NDKVV ccc KdG GVP........AKNLPKYLQQFKN...K..PS ccc KdG VGGVQQVDFE c B AI c B NAL c B KP cccc KddddG DLII cc IS.G...R c B QSKFYDKL c B KEI cccc KdddG APTL c FVGLD.NANFLSS c B FENNVLSV c B AK cc KG LYGLE c B ..KEA c B LEKI c B SDIK IPISMSDE.....GDSFLV BcBcKK DH .Q .L SD IK GBcNBcEG NT KK IBcVBcPP KK NN PBcPBcSK KKddG cc VV ccIcVcLF DD LF GG IS LL DBcDBcTT FL DD AK LBcLBcKG LBcLBcND DD KI VV VKdG ccc GVP........AKNLPKYLQQFKN...K..PS ccc KdG VGGVQQVDFE BcBcAK IBcVBcNA AE LBcLBcKD PKddddG cccc DLII cc IS.G...R BcBcQQ SS KE FS YY DK KE LBcFBcKS EK IKdddG cccc APTL ccFY VL GG LV DD .. NT AA NK FY LX SE SBcSBcFF EK NS ND VA LE ST VBcIBcAG KKG cc LYGLE BcBc.. .. KD EK ABcVBcLK ED KE IBcLBcSA DN II KBcDBc SSKGSDTK.....KEQITV cc KddG K VV ccc KdG A GLP........KQVLPKYLSKFKD...DKYAD ccc KdG VGSLKEPDFD cccc KddddG P DLII cc IS.A...R cccc KdddG I APTI cc KG K IFDKE .....GSA.....PTEVTI BcBc.D .P KV SY SE LE DBcTBcET VV KE LBcVBcSP KV VD PBcPBcEQ KKddG cc IV ccTcVcFF DD LX GA AA AL DBcDBcTT II RG AA LBcLBcGG FBcGBcA. K. NE II VKdG ccc GMP........TKTVPTYLKDLVG...T.VKN ccc KdG VGSMKEPDLE BcBcAA IBcIBcAE AA LBcQBcEQ PKddddG cccc DLII cc AS.P...R BcBcTS QS KG FL VW DA KD FBcLBcKN EE IKdddG cccc APTV ccLD FL QS AL SR .. K. DG DS YY WL TD SBcTBcTL KE AQ NN IT ET SF LBcLBcAG SKG cc AFGET BcBcG. T. QA KE ABcABcKE ES EV LBcLBcAA KE LL DBcEBc TPATASYTWDRNTATEEGA cc KddG R IV ccc KdG A GAP........LDSVPDYLEEYLA...DDAFN ccc KdG AGTLFEADLI cccc KddddG P DLIV cc VG.G...R cccc KdddG I APTI cc KG K VLGAE .............METVTI BcBcEK HD .. .. RE LN GBcGBcKT TV TK LBcVBcEP QK KD PBcABcQK RKddG cc VV ccVcVcIL GE VY GS AF LA DBcDBcAA IL DA SA FBcLBcGD IBcVBcE. P. VK AP VKdG ccc S.K........FDGTPDYLAKYKS...DKYPS ccc KdG AGSLFEPDFE BcBcTE IBcIBcYS TK QBcLBcKK PKddddG cccc DLIV cc IG.P...R BcBcAH SK KG SI YN DK EE LBcLBcSN KK IKdddG cccc APTI ccVS FL AK AS EF A. D. QD GG YD WY EK SBcQBcTN QI QN QS WF RK NT LBcIBcGA KKG cc VFAIE BcBcP. A. .K .E VBcGBcEE AK KR IBcLBcEA QE VH DBcDBc .........GSHMASTISV cc KddG R IV ccc KdG V GIA........DDGKKKRIIKPVREKIGDYTS ccc KdG VGTRKQPNLE cccc KddddG P DLII cc ADSS...R cccc KdddG I APTL cc KG K ALNKE NKEESTKEDNKKE..VVTV BcBcEK HD .. .. AE MN GBcGBcKT TV EK VBcVBcPP AK ND PBcABcKK RKddG cc VV ccIcVcLL TE NY ES GF TA EBcDBcAA LL LA EA LBcLBcGD VBcVBc.. .. KK PP VKdG ccc GAV........KSWTGDPWYPHIKDKMKDVKV ccc KdG VGDEGQVNVE BcBcTE IBcIBcAS SK LBcLBcKK PKddddG cccc DLII cc GNKM...R BcBcHH EK KG VI YN EK QE LBcLBcKN AK IKdddG cccc APTV ccFS SL EK TS LF .. .. RD GG ED WY KK DBcQBcNN .I .N .S FF KK FT YBcIBcAA KKG cc ALNKE BcBc.. .. KK EE GBcGBcQE KK VR VBcLBcAA DE YH EBcDBc .........GSHXASTISV cc KddG R IV ccc KdG V GIA........DDGKKKRIIKPVREKIGDYTS ccc KdG VGTRKQPNLE cccc KddddG P DLII cc ADSS...R cccc KdddG I APTL cc KG K ALNKE IAAVQAADWPRQI...... BcBc.. .. TK DA SE RN GBcGBcTN HV TK LBcIBcEP SK QH PBcPBcQK RKddG cc IV ccScVcTX SA VD TG LY TY GBcGBcSY LF LK AT IBcLBcDG ABcIBcP. V. IN AV SKdG ccc GATTPNNRVADDQGFLRQWSKVAK...ERKLQ ccc KdG RLYIGEPSAE BcBcAK VBcVBcAI AD QBcLBcMN PKddddG cccc DLIL cc ISATGGDS BcBcAQ LG AA LD YI DK QK LBcLBcSE TK IKdddG cccc APTL ccIA IV NK YY DD .K .. DL KD SN WI QE SBc.BcL. .. .. .Q LL TK QE LBcFBcGA EKG cc ITGHE BcBc.. .. KD QK ABcABcAE EK RW IBcLBcAA QK FW DBcDBc ..ESKGSASDSKGAETFTY cc KddG R VV ccc KdG V GAP........ENVFKNPYYKGKT...NGVEN ccc KdG IGD..GTSVE cccc KddddG P DLII cc VW.T...T cccc KdddG I APTV cc KG K XTGTE .........GSHM..TTSI CcK H --c ..AMG CcT T E ICccc KGKP CcK RJIIH ccV VcTcL Y Q G A T DCcV A cc VSL CccG MMMMMMMMM--------M Ccc. c. cK P cVJIH V ccc GAV........ESWTQKPKFEYIKNDLKDTKI ccc JIH VGQEPAPNLE CcE ICcS K LCcK PJIIIIH cccc DLIV ccA cSKV...R CcN E K V Y D Q LCcS K IJIIIH cccc APTV cS T D T V --ccc ..F.KFKD CcT . . . T K L MCcG cKJH ccA L cG cK cECc. . c K MMMMMMMMMM

EA CcE D L LCcK K Y DCc cccccccc----LMMMMMM ----- c c c ------cc -----MMMMMMMM--MMM cccMcMMMMMMMMMMMMMMMMMMMMMM c cc --------ccMMM -------cc cMMMMM c cc cM---M--MMMMMMMMMMMMMMMMM c-----c-----cc cc cc cccc ccccMMMMMMM-M---MMMMMMMMMMMMMMMMMMMMM-MMMMMMMMMMMMMMMMMMMMMM -c -c-----c ccc cc ccc c c ccc--ccc cc c c ccc cc c

30

2CHU_A 3ZK3_A 3ZKW_B 3GFV_A 4JCC_A 4MX8_A 3TEF_A 3EIW_A 3TNY_A 3EIX_A 3TLK_A 3HXP_A 3MWF_A acc hyd 2CHU_A 2CHU_A 3ZK3_A 3ZKW_B 3GFV_A 4JCC_A 4MX8_A 3TEF_A 3EIW_A 3TNY_A 3EIX_A 3TLK_A 3HXP_A 3MWF_A

cccccccc A

40

cccccccc A

60

70

80

cccccccccccccccccccccccccccccccccccccc

90

ccccccccccccc A

100

c

110

120

ccccccccccccccccccccccccc c "c "c

130

140

150

160

ccccccccccccccccccccc ccccccccccccccc ccccccc c" "c c B

170

cc ccccccccc

c : c O :

β8 β9 α6 β10 β11 α7 β12 α8 η5 α9 β13 α10 α11 iiiiiiii jjjjjjjk iiii jk jjk iiiiiii jjjjjk iiii lll iiii jjjk iiii iiiiiiiiiiiiiii T..T T T jjjjk T T iiiiiii jjjjjjjk jjjjk iiii jk jjk iiiiiii jjjjjkiiiii iiii iiii iiii jjjk iiii iiiiiiiiiiiiiii S TT T..T TT TT iiiiiii jjjjjjjk iiii jk jjk iiiiiii jjjjjkiiiii iiii iiii iiii jjjk iiii iiiiiiiiiiiii T T jjjjk T T TT iiiiiiiiiiiii jjjjjjjk jjjjk iiii jk jjk iiiiiii jjjjjkiiiii iiiii lll iiii jjk iiiiii iiiiiiiiiiiiiiii Siiiiiiiiiii S S SS TT TT TT jjjjjjjk jk i iii jjjjjkiiii llll iiii iiiiii iiiiiiiiiiilll Siiii S S iiii iiii S jjk S T T jjjjk T T jk iiiiiii iiiiiiiiiiiii jjjjjjk jjjk iiiiiiii i iiiiiii jjjjjkiiiii lll iiii jjjk iiiii iiiiiiiiiiilllll S TT ..... iiiiiiiiiiii jjjjjjjk iiii jk ii. . . . iii. . .llljk jjjjjk iiii iiiii iiii iiii jjk iiii S iiiiiiiiiiiii T T jjjjk T T T T jk iiiiiii iiiiiiiii jjjjjjk jjjk iiiiiiii jjj k iiiiiii jjjjjkl ll iiiiiiii iiii iiii jjjjkiiii iiiiiiiiiiiiiiii S S TT TT .... . iiiiii iiiiiiiii llll jkllljkT T jjj. k lllllll jjjjjk i. . iiiiiiiii iiii iiii jjk iiii iiiiiiiiiiiiiii S . . . . iiiilllll jjjjjjkT T jjjjk iiiiiiiii jjjjjjk jjjk iiiiiiii ii iii iiiiiii jjjjjkl ll iiiiiiii iiiii iiii jjjjkiiii iiiiiiiiiiiiiiii S S S S jjjjklll i iiiiiiiiiiiiii S TT TT .... TT . iiiiiiiii jjjjjjklll jjjjk iiiiiiii jjjk. Siiiii jjjjk i. . . . . . . . . iiiiiiii lll iiii TT T...T .... iiiiiiiiiiiiii jjjjjjk jjjjk iiiii iiiiiii jjk iiii iiii iiiiiiiiiiiii TT iiiiiiiiiiiiiilll jjjjjk T T jjjk iiiiiiiii iiii. . . . iiii jjjk lllllll jjjjjk T T iiiiiiiiiii iiiii iiii jk iiii iiiiiiiiiiiiii S S S X X X X X X X X X X X X X X NEI c A EKA c A KSI.VDE..DK...KA cccc DEEF LIILTNSNKI c A SA cc DF FGPQ.......S c A RFG c A II c A HDVL cc DF GINAVDENI....KXX........XXGKSI cc DF NSE c A FI c A LEKN ccc DEF PDYI ccc DEF FVVDRNVILGN....KERAQGI c A LD cc DF NALVAKTKA c DF c A QN c A KK c A .I c A IYL cc DF DPEYW c A YLASGNG cc DF LES c A LKTMI c A LE cc DF IKNAVK NEI BcBcEE KK ABcABcKK SS II .. VV DD EE .. .. DD KK .. .. .. KK AKddG cccc LIILTNSNKI BcBcSS AKG cc FGPQ.......S BcBcRR FF GBcGBcII IBcIBcHH DD VV LKG cc GINAVDENI....KVG........THGKSI cc KG NSE BcBcFF IBcIBcLL EE KK NKdG ccc PDYI ccc KdG FVVDRNVILGN....KERAQGI BcBcLL DKG cc NALVAKTKA cKG KG cAcQQ NBcNBcKK KBcKBc.. IBcIBcII YY LKG A cc DPEYW BcBcYY LL AA SS GG NN GKG cc LES BcBcLL KK TT MM IBcIBcLL EKG cc IKNAVK NEI cccc KddG A LIILTNSNKI cc KG A FGPQ.......S cc KG L GINAVDENI....KVG........THGKSI cc KG NSE ccc KdG N PDYI ccc KdG FVVDRNVILGN....KERAQGI cc KG D NALVAKTKA c cc KG L DPEYW cc KG G LES cc KG E IKNAVK HSI c B ADV c B KKTAEKL..NK...NG cccc KddG LVIXANDGKI c B SA cc KG FGPK.......S c B RYG c B LI c B HDVF cc KG GVAPADQNI....KAS........THGQSV cc KG SYE c B YI c B SKTN ccc KdG PDYL ccc KdG FVIDRGTAIGE....TSSTKQV c B VE cc KG NDYVKNVNA c KG c V KN c B GH c B .V c B IYL cc KG DSATW c B YLSG.GG cc KG LES c B XTQXI c B KE cc KG VKDGLE ESI c B QEV c B ATKNESS..DK...KA cccc KddG LAILLNEGKM c B AA cc KG FGAK.......S c B RFS c B FL c B YQTL cc KG KFKPTDTKF....EDS........RHGQEV cc KG SFE c B SV c B KEIN ccc KdG PDIL ccc KdG FVINRTLAIGGD...NSSNDGV c B LE cc KG NALIAETPA c KG c A KN c B GK c B .I c B IQL cc KG TPDLW c B YLSG.GG cc KG LES c B TKLMI c B ED cc KG IQKALK AGI c B AEA c B KAAVTEA..SG...TG cccc KddG LGIXVSGGQL c B SA cc KG LSPNTGNDPRGA c B RGG c B LI c B YDVF cc KG GVQPVLEDI....KAA........THGEPI cc KG SFE c B FL c B LEHD ccc KdG PQWL ccc KdG WVVDRDAATGAE..GAQAAKVV c B LD cc KG NEIVNRTTA c KG c A TE c B DH c B .V c B LYL cc KG NPTAW c B YIVF.GG cc KG VET c B TRIXI c B DD cc KG VLQVAA AQF c B KSI c B MQYNQQH..KS...DA cccc KddG MLVMSSGGNL c B TT cc KG FGAN.......S c B RFS c B SV c B YKDF cc KG GFSETVPVS....KES........SHGDLI cc KG SFE c B YI c B REHN ccc KdG PKTL ccc KdG LVVDRDKVVTKG...ETNIRQT c B FE cc KG NDLVKATTA c KG c Y KN c B GH c B .I c B AYL cc KG DVNAW c B YIAI.SG cc KG VKA c B TEQMV c B AD cc KG MKASVG KLI c B NKY c B KDEIKFDRN....QKV cccc KddG LPAVVAKAGL c B LA cc KG HPNY.......S c B YVG c B QF c B LNEL cc KG GFKNALSDD....VTKGLSKYLKGPYLQ.L cc KG DTE c B HL c B ADLN ccc KdG PERM ccc KdG IIMTD.HAKKDS....AEFKKL c B QE cc KG DATWKKLNA c KG c V KN c B NR c B .V c B DIV cc KG DRDVW c B ARSR..G cc KG LIS c B SEEMA c B KE cc KG LVELSK SRM c B KDL c B ....KGKLGDKVNQEI cccc KddG SMVRFMPGDV c B RI cc KG YHGD.......T c B FSG c B VI c B LKEL cc KG GFKRPGDQN....KDDFAE........RNV cc KG SKE c B RI c B SAMD ccc KdG GDVL ccc KdG FYFTFDKGNEKK..GSELEKEY c B IN cc KG DPLFKNLNA c KG c V KN c B GK c B .A c B YKV cc KG DDVIW c B NTAG..G cc KG VIA c B ANLLL c B DD cc KG IEKRFV KLI c B NKY c B KDEIKFDRN....QKV cccc KddG LPAVVAKAGL c B LA cc KG HPNY.......S c B YVG c B QF c B LNEL cc KG GFKNALSDD....VTKGLSKYLKGPYLQ.L cc KG DTE c B HL c B ADLN ccc KdG PERX ccc KdG IIXTD.HAKKDS....AEFKKL c B QE cc KG DATWKKLNA c KG c V KN c B NR c B .V c B DIV cc KG DRDVW c B ARSR..G cc KG LIS c B SEEXA c B KE cc KG LVELSK KQL c B AAA c B KEQIKLPPQ...PVTA cccc KddG IVYTAAAHSA c B NL cc KG WTPE.......S c B AQG c B QM c B LEQL cc KG GFTLAKLPAGLNASQSQ...GKRHDIIQLG cc KG GEN c B LA c B AGLN ccc KdG GESL ccc KdG FLFAGDQ.........KDADAI c B YA cc KG NPLLAHLPA c KG c V QN c B KQ c B .V c B YAL cc KG GTETF c B RLDY... cc KG .YS c B AMQVL c B DR cc KG LKALFL KKV c B AAA c B KTKIKKAVGDK...TI cccc KddG SIXQTNGKDI c B YV cc KG FGKDF.....GR c B GGS c B II c B YKDL cc KG GLQATKLTKEKAIDQG........PGYTSI cc KG SLE c B KL c B PDFA ccc KdG GDYI ccc KdG FAGPWQS........GGDDGGV c B FE cc KG SSIWKNLNA c KG c V KN c B GH c B .V c B YKX cc KG DPIGF c B YFTDPIS cc KG LEG c B QLEFI c B TE cc KG DKV CcA A FCcQ K D -A K cA c-KYKDAWPLKA cccc JIIH SVVNFRADHT CcR IJH ccY A G . ------.......G CccY A GCcE ICccL cN cD LJH cccG F cK ccc RNKDLQ....KQVDNG....KDIIQLT ccS K ECcS ICcP L cc JH MN ccc JIH ADHI ccc JIH FVVKSDPNAKDAALVKKTESEW CcT SJH ccS K E W K N L cD AJH ccVcccc KN CcN c-ccc Cc- -V SCcD D LJH Q cccccc DEITW CcN L A cG . . GJH ccY cK SCcS cL cK L ICccc DD ccSL cLY cTE c KK LL c EN JH cc cc ccc-c MMMMMMMMM-MM -- c----c --MM---MMMMMMMMMMMMMMMMMM-------MMMMMMMMMMMMMMMMMM ---c --cccc c c cc------ccc c cccccccc ccMMMMMMMMMMMMMMMMM MMMMMMMMMM c c ccccc cMMMMMMMMMMMMM cc ccc cccc ccMMMMMMMM-MMMMMMMMMMMMMMMMMMMMMMMMMMMMMMMN

180

2CHU_A 3ZK3_A 3ZKW_B 3GFV_A 4JCC_A 4MX8_A 3TEF_A 3EIW_A 3TNY_A 3EIX_A 3TLK_A 3HXP_A 3MWF_A acc hyd 2CHU_A

50

ccccccccc ccc

B : O

Kept ligands ZN: ECA" FE*

190

cc :B O

200

cccccccccccccccccc

210

220

ccccccccccccccccccc "c A

230

c

240

250

cccccccccccccccccccccccccccc "c

260

270

280

290

300

310

ccccccccccccccccccccccc cccccccccccccccccccccccccc ccc ccc

AA *c

B