Structure of PDB 8eop Chain A Binding Site BS01

Receptor Information

>8eop Chain A (length=1687) Species: 9606 (Homo sapiens)

AFWTQLMLLLWKNFMYRRRQPVQLLVELLWPLFLFFILVAVRHSHPPLEH
HECHFPNKPLPSAGTVPWLQGLICNVNNTCFPQLTPGEEPGRLSNFNDSL
VSRLLADARTVLGGASAHRTLAGLGSLLEAAEDLAQELLALRSLVELRAL
LQRPRGTSGPLELLSEALCSVSPACSELIGALDSHPLSRLLWRRLKPLIL
GKLLFAPDTPFTRKLMAQVNRTFEELTLLRDVREVWEMLGPRIFTFMNDS
SNVAMLQRLLQMALRSFLDPGSGGYSWQDAHADVGHLVGTLGRVTECLSL
DKLEAAPSEAALVSRALQLLAEHRFWAGVVFLGPETPDLGPGHVRIKIRM
DIDVVTRTNKIRDRFWDPGPAADPLTDLRYVWGGFVYLQDLVERAAVRVL
SGANPRAGLYLQQMPYPCYVDDVFLRVLSRSLPLFLTLAWIYSVTLTVKA
VVREKETRLRDTMRAMGLSRAVLWLGWFLSCLGPFLLSAALLVLVLKLGD
ILPYSHPGVVFLFLAAFAVATVTQSFLLSAFFSRANLAAACGGLAYFSLY
LPYVLCVAWRDRLPAGGRVAASLLSPVAFGFGCESLALLEEQGEGAQWHN
VGTRPTADVFSLAQVSGLLLLDAALYGLATWYLEAVCPGQYGIPEPSPGV
SVRSLEKRFPGSPQPALRGLSLDFYQGHITAFLGHNGAGKTTTLSILSGL
FPPSGGSAFILGHDVRSSMAAIRPHLGVCPQYNVLFDMLTVDEHVWFYGR
LKGLSAAVVGPEQDRLLQDVGLVSKQSVQTRHLSGGMQRKLSVAIAFVGG
SQVVILDQPTAGVDPASRRGIWELLLKYREGRTLILSTHHLDEAELLGDR
VAVVAGGRLCCCGSPLFLRRLEEIFLKVVEECAGRVQGWALTRQQLQALL
LKRFLLARRSRRGLFAQIVLPALFVGLALVFSLIVPPFGHYPALRLSPTM
YGAQVSFFSEDAPGDPGRARLLEALLQEAGLEEPPVQHSSHRFSAPEVPA
EVAKVLASGNWTPESPSPACQCSRPGARRLLPDCPAAAGGPPPPQAVTGS
GEVVQNLTGRNLSDFLVKTYPRLVRQGLKTKKWVNEVRYGGFSLGGRDPG
LPSGQELGRSVEELWALLSPLPGGALDRVLKNLTAWAHSLDAQDSLKIWF
NNKGWHSMVAFVNRASNAILRAHLPPGPARHAHSITTLNHPLNLTKEQLS
EGALMASSVDVLVSICVVFAMSFVPASFTLVLIEERVTRAKHLQLMGGLS
PTLYWLGNFLWDMCNYLVPACIVVLIFLAFQQRAYVAPANLPALLLLLLL
YGWSITPLMYPASFFFSVPSTAYVVLTCINLFIGINGSMATFVLELFSDQ
KLQEVSRILKQVFLIFPHFCLGRGLIDMVRNQAMADAFERLGDRQFQSPL
RWEVVGKNLLAMVIQGPLFLLFTLLLQHRSQDEDVARERERVVQGATQGD
VLVLRNLTKVYRGQRMPAVDRLCLGIPPGECFGLLGVNGAGKTSTFRMVT
GDTLASRGEAVLAGHSVAREPSAAHLSMGYCPQSDAIFELLTGREHLELL
ARLRGVPEAQVAQTAGSGLARLGLSWYADRPAGTYSGGNKRKLATALALV
GDPAVVFLDQPTTGMDPSARRFLWNSLLAVVREGRSVMLTSHSMEECEAL
CSRLAIMVNGRFRCLGSPQHLKGRFLEEVFLYFSKDQ

Ligand information

• Ligand ID: ATP
• InChI: InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1
• InChIKey: ZKHQWZAMYRWXGA-KQYNXXCUSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N
  CACTVS 3.341: Nc1ncnc2n(cnc12)[CH]3O[CH](CO[P](O)(=O)O[P](O)(=O)O[P](O)(O)=O)[CH](O)[CH]3O
  ACDLabs 10.04: O=P(O)(O)OP(=O)(O)OP(=O)(O)OCC3OC(n2cnc1c(ncnc12)N)C(O)C3O
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@@](=O)(O)O[P@](=O)(O)OP(=O)(O)O)O)O)N
  CACTVS 3.341: Nc1ncnc2n(cnc12)[C@@H]3O[C@H](CO[P@](O)(=O)O[P@@](O)(=O)O[P](O)(O)=O)[C@@H](O)[C@H]3O
• Formula: C10 H16 N5 O13 P3
• Name: ADENOSINE-5'-TRIPHOSPHATE
• ChEMBL: CHEMBL14249
• DrugBank: DB00171
• ZINC: ZINC000004261765
• PDB chain: 8eop Chain A Residue 2207

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8eop Cryo-EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms.
• Resolution: 3.7 Å
• Binding residue (original residue number in PDB): H939 S941 Y1802 N1829 G1830 G1832 K1833 S1835 Q1874
• Binding residue (residue number reindexed from 1): H782 S784 Y1461 N1488 G1489 G1491 K1492 S1494 Q1533
• Annotation score: 5

Enzymatic activity

• Enzyme Commision number: 7.6.2.1: P-type phospholipid transporter.

Gene Ontology

Molecular Function

• GO:0005524 ATP binding
• GO:0005548 phospholipid transporter activity
• GO:0016887 ATP hydrolysis activity
• GO:0034188 apolipoprotein A-I receptor activity
• GO:0042626 ATPase-coupled transmembrane transporter activity
• GO:0090554 phosphatidylcholine floppase activity
• GO:0090556 phosphatidylserine floppase activity
• GO:0140326 ATPase-coupled intramembrane lipid transporter activity
• GO:0140328 floppase activity
• GO:0140359 ABC-type transporter activity

Biological Process

• GO:0006869 lipid transport
• GO:0006909 phagocytosis
• GO:0007613 memory
• GO:0008542 visual learning
• GO:0010875 positive regulation of cholesterol efflux
• GO:0018149 peptide cross-linking
• GO:0019216 regulation of lipid metabolic process
• GO:0033344 cholesterol efflux
• GO:0033700 phospholipid efflux
• GO:0034205 amyloid-beta formation
• GO:0034380 high-density lipoprotein particle assembly
• GO:0034504 protein localization to nucleus
• GO:0038027 apolipoprotein A-I-mediated signaling pathway
• GO:0042985 negative regulation of amyloid precursor protein biosynthetic process
• GO:0043409 negative regulation of MAPK cascade
• GO:0044857 plasma membrane raft organization
• GO:0045332 phospholipid translocation
• GO:0045806 negative regulation of endocytosis
• GO:0050766 positive regulation of phagocytosis
• GO:0055085 transmembrane transport
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0150094 amyloid-beta clearance by cellular catabolic process
• GO:1900223 positive regulation of amyloid-beta clearance
• GO:1901076 positive regulation of engulfment of apoptotic cell
• GO:1902430 negative regulation of amyloid-beta formation
• GO:1902991 regulation of amyloid precursor protein catabolic process
• GO:1902995 positive regulation of phospholipid efflux
• GO:1903898 negative regulation of PERK-mediated unfolded protein response
• GO:2000010 positive regulation of protein localization to cell surface

Cellular Component

• GO:0000139 Golgi membrane
• GO:0001891 phagocytic cup
• GO:0005737 cytoplasm
• GO:0005768 endosome
• GO:0005783 endoplasmic reticulum
• GO:0005794 Golgi apparatus
• GO:0005886 plasma membrane
• GO:0009986 cell surface
• GO:0016020 membrane
• GO:0030054 cell junction
• GO:0031901 early endosome membrane
• GO:0032587 ruffle membrane
• GO:0042995 cell projection
• GO:0043231 intracellular membrane-bounded organelle
• GO:0097386 glial cell projection

External links

• PDB: RCSB:8eop, PDBe:8eop, PDBj:8eop
• PDBsum: 8eop
• PubMed: 36484366
• UniProt: Q8IZY2|ABCA7_HUMAN Phospholipid-transporting ATPase ABCA7 (Gene Name=ABCA7)