Structure of PDB 8el1 Chain B Binding Site BS03

Receptor Information

>8el1 Chain B (length=515) Species: 9606,83333

IEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVA
ATGDGPDIIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNG
KLIAYPIAVEALSLIYNKDLLPNPPKTWEEIPALDKELKAKGKSALMFNL
QEPYFTWPLIAADGGYAFKYENGKYDIKDVGVDNAGAKAGLTFLVDLIKN
KHMNADTDYSIAEAAFNKGETAMTINGPWAWSNIDTSKVNYGVTVLPTFK
GQPSKPFVGVLSAGINAASPNKELAKEFLENYLLTDEGLEAVNKDKPLGA
VALKSYEEELAKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINAA
SGRQTVDEALKDAQTGSELYRQSLEIISRYLREQATGAADTAPMGASGAT
SRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFS
DGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDW
LVKQRGWDGFVEFFH

Ligand information

• Ligand ID: WME
• InChI: InChI=1S/C53H51Cl2FN6O9S/c1-30-43-31(2)47(55)48(46(30)54)70-39(24-62-18-16-61(3)17-19-62)27-68-38-12-13-41(69-25-36-14-15-57-50(60-36)33-6-10-37(11-7-33)67-28-40-26-65-20-21-66-40)34(22-38)23-42(53(63)64)71-51-45-44(43)49(72-52(45)59-29-58-51)32-4-8-35(56)9-5-32/h4-15,22,29,39-40,42H,16-21,23-28H2,1-3H3,(H,63,64)/t39-,40-,42-/m1/s1
• InChIKey: BOMNURVTAHAEBQ-KWIIHVIGSA-N
• SMILES:
  CACTVS 3.385: CN1CCN(CC1)C[C@@H]2COc3ccc(OCc4ccnc(n4)c5ccc(OC[C@H]6COCCO6)cc5)c(C[C@@H](Oc7ncnc8sc(c9ccc(F)cc9)c(c%10c(C)c(Cl)c(O2)c(Cl)c%10C)c78)C(O)=O)c3
  ACDLabs 12.01: CN1CCN(CC1)CC1Oc2c(Cl)c(C)c(c3c4c(ncnc4sc3c3ccc(F)cc3)OC(Cc3cc(OC1)ccc3OCc1ccnc(n1)c1ccc(OCC3COCCO3)cc1)C(=O)O)c(C)c2Cl
  OpenEye OEToolkits 2.0.7: Cc1c-2c(c(c(c1Cl)OC(COc3ccc(c(c3)CC(Oc4c5c2c(sc5ncn4)c6ccc(cc6)F)C(=O)O)OCc7ccnc(n7)c8ccc(cc8)OCC9COCCO9)CN1CCN(CC1)C)Cl)C
  OpenEye OEToolkits 2.0.7: Cc1c-2c(c(c(c1Cl)O[C@@H](COc3ccc(c(c3)C[C@@H](Oc4c5c2c(sc5ncn4)c6ccc(cc6)F)C(=O)O)OCc7ccnc(n7)c8ccc(cc8)OC[C@H]9COCCO9)CN1CCN(CC1)C)Cl)C
  CACTVS 3.385: CN1CCN(CC1)C[CH]2COc3ccc(OCc4ccnc(n4)c5ccc(OC[CH]6COCCO6)cc5)c(C[CH](Oc7ncnc8sc(c9ccc(F)cc9)c(c%10c(C)c(Cl)c(O2)c(Cl)c%10C)c78)C(O)=O)c3
• Formula: C53 H51 Cl2 F N6 O9 S
• Name: (7R,16R)-19,23-dichloro-10-{[2-(4-{[(2R)-1,4-dioxan-2-yl]methoxy}phenyl)pyrimidin-4-yl]methoxy}-1-(4-fluorophenyl)-20,22-dimethyl-16-[(4-methylpiperazin-1-yl)methyl]-7,8,15,16-tetrahydro-18,21-etheno-13,9-(metheno)-6,14,17-trioxa-2-thia-3,5-diazacyclononadeca[1,2,3-cd]indene-7-carboxylic acid
• PDB chain: 8el1 Chain B Residue 4000

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8el1 Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models, associated with cardiac troponin increases in patients
• Resolution: 2.406 Å
• Binding residue (original residue number in PDB): H224 A227 F228 M231 M250 V253 G262 R263 T266 L267 F270 F319
• Binding residue (residue number reindexed from 1): H419 A422 F423 M426 M445 V448 G457 R458 T461 L462 F465 F514
• Annotation score: 1

Gene Ontology

Molecular Function

• GO:0005515 protein binding
• GO:0015144 carbohydrate transmembrane transporter activity
• GO:1901982 maltose binding

Biological Process

• GO:0006974 DNA damage response
• GO:0008643 carbohydrate transport
• GO:0015768 maltose transport
• GO:0034219 carbohydrate transmembrane transport
• GO:0034289 detection of maltose stimulus
• GO:0042956 maltodextrin transmembrane transport
• GO:0042981 regulation of apoptotic process
• GO:0055085 transmembrane transport
• GO:0060326 cell chemotaxis

Cellular Component

• GO:0016020 membrane
• GO:0030288 outer membrane-bounded periplasmic space
• GO:0042597 periplasmic space
• GO:0043190 ATP-binding cassette (ABC) transporter complex
• GO:0055052 ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing
• GO:1990060 maltose transport complex

External links

• PDB: RCSB:8el1, PDBe:8el1, PDBj:8el1
• PDBsum: 8el1
• PubMed: 37880389
• UniProt: P0AEX9|MALE_ECOLI Maltose/maltodextrin-binding periplasmic protein (Gene Name=malE);
  Q07820|MCL1_HUMAN Induced myeloid leukemia cell differentiation protein Mcl-1 (Gene Name=MCL1)