The PKA structure has twomain lobes (subdomains).Huse and Kuriyan, 2002αβγThe three phosphates of adenosine tri-phosphate are labeledα, β, and γSchematized PKA structureHuse and Kuriyan, 2002The phosphate binding loop contains aconserved glycine-rich sequence motif.Phosphatebinding loop(P loop)Huse and Kuriyan, 2002Protein Kinase Domain Alignments (all of the N lobe, part of the C lobe) < 1> P loop <-- 2--> <-- 3--><- B-> A002101_Rsk3 43 ISNHVKEGFEKADPSQFELLKVLGQGSYGKVFLVRKVTGSDAGQLYAMKVLKKATLKVRD A001562_Msk1 32 RTANLTGHAEKVGIENFELLKVLGTGAYGKVFLVRKISGHDAGKLYAMKVLKKATIVQKA A001298_Jnk3 48 FYSVEVGDSTFTVLKRYQNLKPIGSGAQG------IVCAAYDAVLDRNVAIKKLSRPFQN A001296_Jnk1 10 FYSVEIGDSTFTVLKRYQNLKPIGSGAQG------IVCAAYDAILERNVAIKKLSRPFQN A001454_Map4k3 1 -MNPGFDLSRRNPQEDFELIQRIGSGTYG------DVYKARNVNTGELAAIKVIKLEPGE A001144_Hpk1 1 MALVDPDIFNKDPREHYDLLQRLGGGTYG------EVFKARDKVSKDLVALKMVKMEPDD A001506_Mek2 56 AFLTQKAKVGELKDDDFERISELGAGNGG------VVTKARHRPSGFIMARKLIHLEIKP A001561_Mrcka 61 KPFTSKVKQMRLHREDFEILKVIGRGAFG---EVAVVKLKNADKVFAMKILNKWEMLKRA (K72 in PKA) <--- C------> <- 4-> <- 5-> <--- D---> A002101_Rsk3 103 R--VRSKMERDILAEVN-HPFIVKLHYAFQTEGKLYLILDFLRGGDLFTR---LSKEVMF A001562_Msk1 92 KTTEHTRTERQVLEHIRQSPFLVTLHYAFQTETKLHLILDYINGGELFTH---LSQRERF A001298_Jnk3 102 QTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMEL A001296_Jnk1 64 QTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMEL A001454_Map4k3 54 D--FAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIY---HVTGPL A001144_Hpk1 55 D--VATLQKEILMLKTCRHANIVAYHGSYLWLQKLWICMEFCGAGSLQDIY---QVTGSL A001506_Mek2 110 -AVRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVL---KEAKRI A001561_Mrcka 118 ETACFREERDVLVNGD--SKWITTLHYAFQDDNNLYLVMDYYVGGDLLTLLS--KFEDRL (E91 in PKA) <--------- E--------> < 6> <- 7-> <- 8-> < 9>------ A002101_Rsk3 157 TEEDVKFYLAELALALDHLHGL-GIIYRDLKPENILLDEEGHIKITDFGLSKEAT-DHDK A001562_Msk1 149 TEHEVQIYVGEIVLALEHLHKL-GIIYRDIKLENILLDSNGHVVLTDFGLSKEFVADETE A001298_Jnk3 162 DHERMSYLLYQMLCGIKHLHSA-GIIHRDLKPSNIVVKSDCTLKILDFGLARTAG--TSF A001296_Jnk1 124 DHERMSYLLYQMLCGIKHLHSA-GIIHRDLKPSNIVVKSDCTLKILDFGLARTAG--TSF A001454_Map4k3 109 SELQIAYVSRETLQGLYYLHSK-GKMHRDIKGANILLTDNGHVKLADFGVSAQIT-ATIA A001144_Hpk1 110 SELQISYVCREVLQGLAYLHSE-KKIHRDIKGANILINDCGEVKLADFGISAQIG-ATLA A001506_Mek2 166 PEDILGKVSIAVLRGLAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLI---DS A001561_Mrcka 174 PEEMARFYLAEMVIAIDSVHQL-HYVHRDIKPDNILMDMNGHIRLADFGSCLKLMEDGTV (D166, N171 in PKA) (D184 in PKA) activation loop <------ F------> A002101_Rsk3 215 RAYSFCGTIEYMAPEVVNR-----RGHTQSADWWSFGVLMFEMLTGS-LPFQGKDRK--- A001562_Msk1 208 RAYSFCGTIEYMAPDIVRGG---DSGHDKAVDWWSLGVLMYELLTGA-SPFTVDGEKNSQ A001298_Jnk3 219 MMTPYVVTRYYRAPEVILG-----MGYKENVDIWSVGCIMGEMVRHK-ILFPGRD----- A001296_Jnk1 181 MMTPYVVTRYYRAPEVILG-----MGYKENVDLWSVGCIMGEMVCHK-ILFPGRD----- A001454_Map4k3 167 KRKSFIGTPYWMAPEVAAVER--KGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRALF A001144_Hpk1 168 RRLSFIGTPYWMAPEVAAVAL--KGGYNELCDIWSLGITAIELAELQPPLFDVHPLRVLF A001506_Mek2 223 MANSFVGTRSYMSPERLQG-----THYSVQSDIWSMGLSLVELAIGR---YPIPP----- A001561_Mrcka 233 QSSVAVGTPDYISPEILQAMEDGKGRYGPECDWWSLGVCMYEMLYGETPFYAESLVETYG Not shown: ~50 amino acids comprising G, H, I and connecting loops between these helices.Kinase activationFig. 12-7 LehnProtein Kinase Domain Alignments (all of the N lobe, part of the C lobe) < 1> P loop <-- 2--> <-- 3--><- B-> A002101_Rsk3 43 ISNHVKEGFEKADPSQFELLKVLGQGSYGKVFLVRKVTGSDAGQLYAMKVLKKATLKVRD A001562_Msk1 32 RTANLTGHAEKVGIENFELLKVLGTGAYGKVFLVRKISGHDAGKLYAMKVLKKATIVQKA A001298_Jnk3 48 FYSVEVGDSTFTVLKRYQNLKPIGSGAQG------IVCAAYDAVLDRNVAIKKLSRPFQN A001296_Jnk1 10 FYSVEIGDSTFTVLKRYQNLKPIGSGAQG------IVCAAYDAILERNVAIKKLSRPFQN A001454_Map4k3 1 -MNPGFDLSRRNPQEDFELIQRIGSGTYG------DVYKARNVNTGELAAIKVIKLEPGE A001144_Hpk1 1 MALVDPDIFNKDPREHYDLLQRLGGGTYG------EVFKARDKVSKDLVALKMVKMEPDD A001506_Mek2 56 AFLTQKAKVGELKDDDFERISELGAGNGG------VVTKARHRPSGFIMARKLIHLEIKP A001561_Mrcka 61 KPFTSKVKQMRLHREDFEILKVIGRGAFG---EVAVVKLKNADKVFAMKILNKWEMLKRA (K72 in PKA) <--- C------> <- 4-> <- 5-> <--- D---> A002101_Rsk3 103 R--VRSKMERDILAEVN-HPFIVKLHYAFQTEGKLYLILDFLRGGDLFTR---LSKEVMF A001562_Msk1 92 KTTEHTRTERQVLEHIRQSPFLVTLHYAFQTETKLHLILDYINGGELFTH---LSQRERF A001298_Jnk3 102 QTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMEL A001296_Jnk1 64 QTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMEL A001454_Map4k3 54 D--FAVVQQEIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIY---HVTGPL A001144_Hpk1 55 D--VATLQKEILMLKTCRHANIVAYHGSYLWLQKLWICMEFCGAGSLQDIY---QVTGSL A001506_Mek2 110 -AVRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVL---KEAKRI A001561_Mrcka 118 ETACFREERDVLVNGD--SKWITTLHYAFQDDNNLYLVMDYYVGGDLLTLLS--KFEDRL (E91 in PKA) <--------- E--------> < 6> <- 7-> <- 8-> < 9>------ A002101_Rsk3 157 TEEDVKFYLAELALALDHLHGL-GIIYRDLKPENILLDEEGHIKITDFGLSKEAT-DHDK A001562_Msk1 149 TEHEVQIYVGEIVLALEHLHKL-GIIYRDIKLENILLDSNGHVVLTDFGLSKEFVADETE A001298_Jnk3 162 DHERMSYLLYQMLCGIKHLHSA-GIIHRDLKPSNIVVKSDCTLKILDFGLARTAG--TSF A001296_Jnk1 124 DHERMSYLLYQMLCGIKHLHSA-GIIHRDLKPSNIVVKSDCTLKILDFGLARTAG--TSF A001454_Map4k3 109 SELQIAYVSRETLQGLYYLHSK-GKMHRDIKGANILLTDNGHVKLADFGVSAQIT-ATIA A001144_Hpk1 110 SELQISYVCREVLQGLAYLHSE-KKIHRDIKGANILINDCGEVKLADFGISAQIG-ATLA A001506_Mek2 166 PEDILGKVSIAVLRGLAYLREKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLI---DS A001561_Mrcka 174 PEEMARFYLAEMVIAIDSVHQL-HYVHRDIKPDNILMDMNGHIRLADFGSCLKLMEDGTV (D166, N171 in PKA) (D184 in PKA) activation loop <------ F------> A002101_Rsk3 215 RAYSFCGTIEYMAPEVVNR-----RGHTQSADWWSFGVLMFEMLTGS-LPFQGKDRK--- A001562_Msk1 208 RAYSFCGTIEYMAPDIVRGG---DSGHDKAVDWWSLGVLMYELLTGA-SPFTVDGEKNSQ A001298_Jnk3 219 MMTPYVVTRYYRAPEVILG-----MGYKENVDIWSVGCIMGEMVRHK-ILFPGRD----- A001296_Jnk1 181 MMTPYVVTRYYRAPEVILG-----MGYKENVDLWSVGCIMGEMVCHK-ILFPGRD----- A001454_Map4k3 167 KRKSFIGTPYWMAPEVAAVER--KGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRALF A001144_Hpk1 168 RRLSFIGTPYWMAPEVAAVAL--KGGYNELCDIWSLGITAIELAELQPPLFDVHPLRVLF A001506_Mek2 223 MANSFVGTRSYMSPERLQG-----THYSVQSDIWSMGLSLVELAIGR---YPIPP----- A001561_Mrcka 233 QSSVAVGTPDYISPEILQAMEDGKGRYGPECDWWSLGVCMYEMLYGETPFYAESLVETYG Not shown: ~50 amino acids comprising G, H, I and connecting loops between these
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