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 | Acetyl CoA | Ligand Info | |||
| Canonical SMILES | CC(=O)SCCNC(=O)CCNC(=O)C(C(C)(C)COP(=O)(O)OP(=O)(O)OCC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)OP(=O)(O)O)O | ||||
| InChI | 1S/C23H38N7O17P3S/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38)/t13-,16-,17-,18+,22-/m1/s1 | ||||
| InChIKey | ZSLZBFCDCINBPY-ZSJPKINUSA-N | ||||
| PubChem Compound ID | 444493 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7LLA Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate (EM map was generated in Cryosparc with non-uniform refinement) | ||||||
| Method | Electron microscopy | Resolution | 2.97 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: 6UI9 Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate | ||||||
| Method | Electron microscopy | Resolution | 3.10 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 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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ASN346
4.583
GLN505
3.712
PHE533
3.086
PHE572
3.341
ALA573
3.372
SER574
2.446
LEU575
4.518
ARG576
2.576
SER577
3.376
ILE597
3.323
ALA598
4.158
GLU599
3.697
ALA624
3.498
|
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| PDB ID: 6UV5 Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate | ||||||
| Method | Electron microscopy | Resolution | 3.40 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 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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SER308
4.231
GLY309
4.451
GLN505
4.292
PHE533
3.369
PHE572
3.324
ALA573
3.399
SER574
3.273
ARG576
3.239
SER577
3.362
ILE597
3.350
ALA598
4.315
GLU599
3.386
ALA624
4.350
|
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| PDB ID: 6Z2H Citryl-CoA lyase module of human ATP citrate lyase in complex with (3S)-citryl-CoA. | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [3] |
| PDB Sequence |
SHMKPASFMT
842 SICDERGQEL852 IYAGMPITEV862 FKEEMGIGGV872 LGLLWFQKRL882 PKYSCQFIEM 892 CLMVTADHGP902 AVSGAHNTII912 CARAGKDLVS922 SLTSGLLTIG932 DRFGGALDAA 942 AKMFSKAFDS952 GIIPMEFVNK962 MKKEGKLIMG972 IGHRVKSINN982 PDMRVQILKD 992 YVRQHFPATP1002 LLDYALEVEK1012 ITTSKKPNLI1022 LNVDGLIGVA1032 FVDMLRNCGS 1042 FTREEADEYI1052 DIGALNGIFV1062 LGRSMGFIGH1072 YLDQKRLKQG1082 LYRHPWDDIS 1092 YVLP
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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 .ACO or .ACO2 or .ACO3 or :3ACO;style chemicals stick;color identity;select .A:933 or .A:934 or .A:935 or .A:936 or .A:938 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:986 or .A:1018 or .A:1020 or .A:1021 or .A:1024 or .A:1025 or .A:1026 or .A:1061 or .A:1065; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ASP933
3.224
ARG934
3.318
PHE935
2.917
GLY936
2.326
ALA938
3.106
LYS968
4.586
LEU969
2.676
ILE970
2.113
MET971
3.339
GLY972
2.040
ILE973
2.769
GLY974
2.336
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Reply to: Acetyl-CoA is produced by the citrate synthase homology module of ATP-citrate lyase. Nat Struct Mol Biol. 2021 Aug;28(8):639-641. | ||||
| REF 2 | Molecular basis for acetyl-CoA production by ATP-citrate lyase. Nat Struct Mol Biol. 2020 Jan;27(1):33-41. | ||||
| REF 3 | Acetyl-CoA is produced by the citrate synthase homology module of ATP-citrate lyase. Nat Struct Mol Biol. 2021 Aug;28(8):636-638. | ||||
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