Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T52189 | Target Info | |||
| Target Name | ATP-citrate synthase (ACLY) | ||||
| Synonyms | Citrate cleavage enzyme; ATP-citrate (pro-S-)-lyase; ACL | ||||
| Target Type | Successful Target | ||||
| Gene Name | ACLY | ||||
| Biochemical Class | Acyltransferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Coenzyme A | Ligand Info | |||
| Canonical SMILES | CC(C)(COP(=O)(O)OP(=O)(O)OCC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)OP(=O)(O)O)C(C(=O)NCCC(=O)NCCS)O | ||||
| InChI | 1S/C21H36N7O16P3S/c1-21(2,16(31)19(32)24-4-3-12(29)23-5-6-48)8-41-47(38,39)44-46(36,37)40-7-11-15(43-45(33,34)35)14(30)20(42-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-31,48H,3-8H2,1-2H3,(H,23,29)(H,24,32)(H,36,37)(H,38,39)(H2,22,25,26)(H2,33,34,35)/t11-,14-,15-,16+,20-/m1/s1 | ||||
| InChIKey | RGJOEKWQDUBAIZ-IBOSZNHHSA-N | ||||
| PubChem Compound ID | 87642 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6UUW Structure of human ATP citrate lyase E599Q mutant in complex with Mg2+, citrate, ATP and CoA | ||||||
| Method | Electron microscopy | Resolution | 2.85 Å | Mutation | Yes | [1] |
| PDB Sequence |
SAKAISEQTG
11 KELLYKFICT21 TSAIQNRFKY31 ARVTPDTDWA41 RLLQDHPWLL51 SQNLVVKPDQ 61 LIKRRGKLGL71 VGVNLTLDGV81 KSWLKPRLGQ91 EATVGKATGF101 LKNFLIEPFV 111 PHSQAEEFYV121 CIYATREGDY131 VLFHHEGGAQ150 KLLVGVDEKL160 NPEDIKKHLL 170 VHAPEDKKEI180 LASFISGLFN190 FYEDLYFTYL200 EINPLVVTKD210 GVYVLDLAAK 220 VDATADYICK230 VKWGDIEFPP240 PFGREAYPEE250 AYIADLDAKS260 GASLKLTLLN 270 PKGRIWTMVA280 GGGASVVYSD290 TICDLGGVNE300 LANYGEYSGA310 PSEQQTYDYA 320 KTILSLMTRE330 KHPDGKILII340 GGSIANFTNV350 AATFKGIVRA360 IRDYQGPLKE 370 HEVTIFVRRG380 GPNYQEGLRV390 MGEVGKTTGI400 PIHVFGTETH410 MTAIVGMALG 420 HRPIPNQPPT430 AGKSTTLFSR495 HTKAIVWGMQ505 TRAVQGMLDF515 DYVCSRDEPS 525 VAAMVYPFTG535 DHKQKFYWGH545 KEILIPVFKN555 MADAMRKHPE565 VDVLINFASL 575 RSAYDSTMET585 MNYAQIRTIA595 IIAQGIPEAL605 TRKLIKKADQ615 KGVTIIGPAT 625 VGGIKPGCFK635 IGNTGGMLDN645 ILASKLYRPG655 SVAYVSRSGG665 MSNELNNIIS 675 RTTDGVYEGV685 AIGGDRYPGS695 TFMDHVLRYQ705 DTPGVKMIVV715 LGEIGGTEEY 725 KICRGIKEGR735 LTKPIVCWCI745 GTCATMFSSE755 VQFGHAGACA765 NQASETAVAK 775 NQALKEAGVF785 VPRSFDELGE795 IIQSVYEDLV805 ANGVIVPAQE815 VPPPTVPMDY 825 SWARELGLIR835 KPASFMTSIC845 DERGQELIYA855 GMPITEVFKE865 EMGIGGVLGL 875 LWFQKRLPKY885 SCQFIEMCLM895 VTADHGPAVS905 GAHNTIICAR915 AGKDLVSSLT 925 SGLLTIGDRF935 GGALDAAAKM945 FSKAFDSGII955 PMEFVNKMKK965 EGKLIMGIGH 975 RVKSINNPDM985 RVQILKDYVR995 QHFPATPLLD1005 YALEVEKITT1015 SKKPNLILNV 1025 DGLIGVAFVD1035 MLRNCGSFTR1045 EEADEYIDIG1055 ALNGIFVLGR1065 SMGFIGHYLD 1075 QKRLKQGLYR1085 HPWDDISYVL1095 PEHM
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| PDB ID: 6UUZ Structure of ACLY in the presence of citrate and CoA | ||||||
| Method | Electron microscopy | Resolution | 3.00 Å | Mutation | No | [1] |
| PDB Sequence |
SAKAISEQTG
11 KELLYKFICT21 TSAIQNRFKY31 ARVTPDTDWA41 RLLQDHPWLL51 SQNLVVKPDQ 61 LIKRRGKLGL71 VGVNLTLDGV81 KSWLKPRLGQ91 EATVGKATGF101 LKNFLIEPFV 111 PHSQAEEFYV121 CIYATREGDY131 VLFHHEGGVD141 VGDVDAKAQK151 LLVGVDEKLN 161 PEDIKKHLLV171 HAPEDKKEIL181 ASFISGLFNF191 YEDLYFTYLE201 INPLVVTKDG 211 VYVLDLAAKV221 DATADYICKV231 KWGDIEFPPP241 FGREAYPEEA251 YIADLDAKSG 261 ASLKLTLLNP271 KGRIWTMVAG281 GGASVVYSDT291 ICDLGGVNEL301 ANYGEYSGAP 311 SEQQTYDYAK321 TILSLMTREK331 HPDGKILIIG341 GSIANFTNVA351 ATFKGIVRAI 361 RDYQGPLKEH371 EVTIFVRRGG381 PNYQEGLRVM391 GEVGKTTGIP401 IHVFGTETHM 411 TAIVGMALGH421 RPIPGKSTTL492 FSRHTKAIVW502 GMQTRAVQGM512 LDFDYVCSRD 522 EPSVAAMVYP532 FTGDHKQKFY542 WGHKEILIPV552 FKNMADAMRK562 HPEVDVLINF 572 ASLRSAYDST582 METMNYAQIR592 TIAIIAEGIP602 EALTRKLIKK612 ADQKGVTIIG 622 PATVGGIKPG632 CFKIGNTGGM642 LDNILASKLY652 RPGSVAYVSR662 SGGMSNELNN 672 IISRTTDGVY682 EGVAIGGDRY692 PGSTFMDHVL702 RYQDTPGVKM712 IVVLGEIGGT 722 EEYKICRGIK732 EGRLTKPIVC742 WCIGTCATQA768 SETAVAKNQA778 LKEAGVFVPR 788 SFDELGEIIQ798 SVYEDLVANG808 VIVPAQEVPP818 PTVPMDYSWA828 RELGLIRKPA 838 SFMTSICDER848 GQELIYAGMP858 ITEVFKEEMG868 IGGVLGLLWF878 QKRLPKYSCQ 888 FIEMCLMVTA898 DHGPAVSGAH908 NTIICARAGK918 DLVSSLTSGL928 LTIGDRFGGA 938 LDAAAKMFSK948 AFDSGIIPME958 FVNKMKKEGK968 LIMGIGHRVK978 SINNPDMRVQ 988 ILKDYVRQHF998 PATPLLDYAL1008 EVEKITTSKK1018 PNLILNVDGL1028 IGVAFVDMLR 1038 NCGSFTREEA1048 DEYIDIGALN1058 GIFVLGRSMG1068 FIGHYLDQKR1078 LKQGLYRHPW 1088 DDISYVLPEH1098 M
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| PDB ID: 6QFB Structure of the human ATP citrate lyase holoenzyme in complex with citrate, coenzyme A and Mg.ADP | ||||||
| Method | X-ray diffraction | Resolution | 3.25 Å | Mutation | No | [2] |
| PDB Sequence |
SAKAISEQTG
11 KELLYKFICT21 TSAIQNRFKY31 ARVTPDTDWA41 RLLQDHPWLL51 SQNLVVKPDQ 61 LIKRRGKLGL71 VGVNLTLDGV81 KSWLKPRLGQ91 EATVGKATGF101 LKNFLIEPFV 111 PHSQAEEFYV121 CIYATREGDY131 VLFHHEGGVD141 VGDVDAKAQK151 LLVGVDEKLN 161 PEDIKKHLLV171 HAPEDKKEIL181 ASFISGLFNF191 YEDLYFTYLE201 INPLVVTKDG 211 VYVLDLAAKV221 DATADYICKV231 KWGDIEFPPP241 FGREAYPEEA251 YIADLDAKSG 261 ASLKLTLLNP271 KGRIWTMVAG281 GGASVVYSDT291 ICDLGGVNEL301 ANYGEYSGAP 311 SEQQTYDYAK321 TILSLMTREK331 HPDGKILIIG341 GSIANFTNVA351 ATFKGIVRAI 361 RDYQGPLKEH371 EVTIFVRRGG381 PNYQEGLRVM391 GEVGKTTGIP401 IHVFGTETHM 411 TAIVGMALGH421 RPIPKSTTLF493 SRHTKAIVWG503 MQTRAVQGML513 DFDYVCSRDE 523 PSVAAMVYPF533 TGDHKQKFYW543 GHKEILIPVF553 KNMADAMRKH563 PEVDVLINFA 573 SLRSAYDSTM583 ETMNYAQIRT593 IAIIAEGIPE603 ALTRKLIKKA613 DQKGVTIIGP 623 ATVGGIKPGC633 FKIGNTGGML643 DNILASKLYR653 PGSVAYVSRS663 GGMSNELNNI 673 ISRTTDGVYE683 GVAIGGDRYP693 GSTFMDHVLR703 YQDTPGVKMI713 VVLGEIGGTE 723 EYKICRGIKE733 GRLTKPIVCW743 CIGTCATMFA768 SETAVAKNQA778 LKEAGVFVPR 788 SFDELGEIIQ798 SVYEDLVANG808 VIVPAQEVPP818 PTVPMDYSWA828 RELGLIRKPA 838 SFMTSICDER848 GQELIYAGMP858 ITEVFKEEMG868 IGGVLGLLWF878 QKRLPKYSCQ 888 FIEMCLMVTA898 DHGPAVSGAH908 NTIICARAGK918 DLVSSLTSGL928 LTIGDRFGGA 938 LDAAAKMFSK948 AFDSGIIPME958 FVNKMKKEGK968 LIMGIGHRVK978 SINNPDMRVQ 988 ILKDYVRQHF998 PATPLLDYAL1008 EVEKITTSKK1018 PNLILNVDGL1028 IGVAFVDMLR 1038 NCGSFTREEA1048 DEYIDIGALN1058 GIFVLGRSMG1068 FIGHYLDQKR1078 LKQGLYRHPW 1088 DDISYVLPE
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| PDB ID: 6HXH Structure of the human ATP citrate lyase holoenzyme in complex with citrate, coenzyme A and Mg.ADP | ||||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | No | [2] |
| PDB Sequence |
SAKAISEQTG
11 KELLYKFICT21 TSAIQNRFKY31 ARVTPDTDWA41 RLLQDHPWLL51 SQNLVVKPDQ 61 LIKRRGKLGL71 VGVNLTLDGV81 KSWLKPRLGQ91 EATVGKATGF101 LKNFLIEPFV 111 PHSQAEEFYV121 CIYATREGDY131 VLFHHEGGVD141 VGDVDAKAQK151 LLVGVDEKLN 161 PEDIKKHLLV171 HAPEDKKEIL181 ASFISGLFNF191 YEDLYFTYLE201 INPLVVTKDG 211 VYVLDLAAKV221 DATADYICKV231 KWGDIEFPPP241 FGREAYPEEA251 YIADLDAKSG 261 ASLKLTLLNP271 KGRIWTMVAG281 GGASVVYSDT291 ICDLGGVNEL301 ANYGEYSGAP 311 SEQQTYDYAK321 TILSLMTREK331 HPDGKILIIG341 GSIANFTNVA351 ATFKGIVRAI 361 RDYQGPLKEH371 EVTIFVRRGG381 PNYQEGLRVM391 GEVGKTTGIP401 IHVFGTETHM 411 TAIVGMALGH421 RPIKSTTLFS494 RHTKAIVWGM504 QTRAVQGMLD514 FDYVCSRDEP 524 SVAAMVYPFT534 GDHKQKFYWG544 HKEILIPVFK554 NMADAMRKHP564 EVDVLINFAS 574 LRSAYDSTME584 TMNYAQIRTI594 AIIAEGIPEA604 LTRKLIKKAD614 QKGVTIIGPA 624 TVGGIKPGCF634 KIGNTGGMLD644 NILASKLYRP654 GSVAYVSRSG664 GMSNELNNII 674 SRTTDGVYEG684 VAIGGDRYPG694 STFMDHVLRY704 QDTPGVKMIV714 VLGEIGGTEE 724 YKICRGIKEG734 RLTKPIVCWC744 IGTCATMFSS754 EVQFGHAGAC764 ANQASETAVA 774 KNQALKEAGV784 FVPRSFDELG794 EIIQSVYEDL804 VANGVIVPAQ814 EVPPPTVPMD 824 YSWARELGLI834 RKPASFMTSI844 CDERGQELIY854 AGMPITEVFK864 EEMGIGGVLG 874 LLWFQKRLPK884 YSCQFIEMCL894 MVTADHGPAV904 SGAHNTIICA914 RAGKDLVSSL 924 TSGLLTIGDR934 FGGALDAAAK944 MFSKAFDSGI954 IPMEFVNKMK964 KEGKLIMGIG 974 HRVKSINNPD984 MRVQILKDYV994 RQHFPATPLL1004 DYALEVEKIT1014 TSKKPNLILN 1024 VDGLIGVAFV1034 DMLRNCGSFT1044 REEADEYIDI1054 GALNGIFVLG1064 RSMGFIGHYL 1074 DQKRLKQGLY1084 RHPWDDISYV1094 LPE
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .COA or .COA2 or .COA3 or :3COA;style chemicals stick;color identity;select .A:261 or .A:262 or .A:309 or .A:347 or .A:505 or .A:533 or .A:572 or .A:573 or .A:574 or .A:575 or .A:576 or .A:577 or .A:597 or .A:598 or .A:599 or .A:624 or .A:625 or .A:626 or .A:664 or .A:964 or .A:969 or .A:970 or .A:973 or .A:974 or .A:1014 or .A:1017 or .A:1018 or .A:1021; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY261
3.503
ALA262
4.797
GLY309
3.817
PHE347
3.790
GLN505
4.035
PHE533
3.446
PHE572
3.634
ALA573
3.871
SER574
2.626
LEU575
4.920
ARG576
2.633
SER577
3.277
ILE597
2.924
ALA598
4.308
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| PDB ID: 6HXM Structure of the citryl-CoA lyase core module of human ATP citrate lyase in complex with citrate and CoASH in space group C2221 | ||||||
| Method | X-ray diffraction | Resolution | 1.30 Å | Mutation | No | [2] |
| PDB Sequence |
MKPASFMTSI
844 CDERGQELIY854 AGMPITEVFK864 EEMGIGGVLG874 LLWFQKRLPK884 YSCQFIEMCL 894 MVTADHGPAV904 SGAHNTIICA914 RAGKDLVSSL924 TSGLLTIGDR934 FGGALDAAAK 944 MFSKAFDSGI954 IPMEFVNKMK964 KEGKLIMGIG974 HRVKSINNPD984 MRVQILKDYV 994 RQHFPATPLL1004 DYALEVEKIT1014 TSKKPNLILN1024 VDGLIGVAFV1034 DMLRNCGSFT 1044 REEADEYIDI1054 GALNGIFVLG1064 RSMGFIGHYL1074 DQKRLKQGLY1084 RHPWDDISYV 1094 LPE
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .COA or .COA2 or .COA3 or :3COA;style chemicals stick;color identity;select .A:933 or .A:934 or .A:935 or .A:936 or .A:937 or .A:938 or .A:964 or .A:968 or .A:969 or .A:970 or .A:971 or .A:972 or .A:973 or .A:974 or .A:975 or .A:976 or .A:1018 or .A:1020 or .A:1021 or .A:1024 or .A:1025 or .A:1026 or .A:1027; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASP933
2.680
ARG934
2.059
PHE935
2.321
GLY936
2.377
GLY937
4.337
ALA938
2.864
LYS964
2.189
LYS968
4.540
LEU969
2.448
ILE970
1.851
MET971
2.572
GLY972
1.995
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| PDB ID: 6HXL Structure of the citryl-CoA lyase core module of human ATP citrate lyase in complex with citrate and CoASH (space group P21) | ||||||
| Method | X-ray diffraction | Resolution | 1.35 Å | Mutation | No | [2] |
| PDB Sequence |
PASFMTSICD
846 ERGQELIYAG856 MPITEVFKEE866 MGIGGVLGLL876 WFQKRLPKYS886 CQFIEMCLMV 896 TADHGPAVSG906 AHNTIICARA916 GKDLVSSLTS926 GLLTIGDRFG936 GALDAAAKMF 946 SKAFDSGIIP956 MEFVNKMKKE966 GKLIMGIGHR976 VKSINNPDMR986 VQILKDYVRQ 996 HFPATPLLDY1006 ALEVEKITTS1016 KKPNLILNVD1026 GLIGVAFVDM1036 LRNCGSFTRE 1046 EADEYIDIGA1056 LNGIFVLGRS1066 MGFIGHYLDQ1076 KRLKQGLYRH1086 PWDDISYVLP 1096 EHM
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .COA or .COA2 or .COA3 or :3COA;style chemicals stick;color identity;select .A:933 or .A:934 or .A:935 or .A:936 or .A:937 or .A:938 or .A:963 or .A:964 or .A:968 or .A:969 or .A:970 or .A:971 or .A:972 or .A:973 or .A:974 or .A:975 or .A:976 or .A:1018 or .A:1020 or .A:1021 or .A:1024 or .A:1025 or .A:1026 or .A:1027; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASP933
2.850
ARG934
2.200
PHE935
3.156
GLY936
2.605
GLY937
4.371
ALA938
2.801
MET963
4.958
LYS964
3.277
LYS968
4.201
LEU969
2.747
ILE970
1.867
MET971
2.510
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Molecular basis for acetyl-CoA production by ATP-citrate lyase. Nat Struct Mol Biol. 2020 Jan;27(1):33-41. | ||||
| REF 2 | Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle. Nature. 2019 Apr;568(7753):571-575. | ||||
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