Structure of PDB 7jww Chain A Binding Site BS01

Receptor Information

>7jww Chain A (length=494) Species: 9606 (Homo sapiens)

DLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDK
EDVDKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATME
SMNGGKLYSNAYLSDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRH
EPIGVCGQIIPWNFPLVMLIWKIGPALSCGNTVVVKPAEQTPLTALHVAS
LIKEAGFPPGVVNIVPGYGPTAGAAISSHMDIDKVAFTGSTEVGKLIKEA
AGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQGQCCIAAS
RIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDL
IESGKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQ
IMKFKSLDDVIKRANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCY
GVVSAQCPFGGFKMSGNGRELGEYGFHEYTEVKTVTVKISQKNS

Ligand information

• Ligand ID: VMG
• InChI: InChI=1S/C22H22N4O2S/c1-15(17-6-4-3-5-7-17)29-22-24-20-19(14-23-25(20)2)21(28)26(22)18-10-8-16(9-11-18)12-13-27/h3-11,14-15,27H,12-13H2,1-2H3/t15-/m1/s1
• InChIKey: ZYDLSTYFDFDODX-OAHLLOKOSA-N
• SMILES:
  CACTVS 3.385: C[CH](SC1=Nc2n(C)ncc2C(=O)N1c3ccc(CCO)cc3)c4ccccc4
  OpenEye OEToolkits 2.0.7: C[C@H](c1ccccc1)SC2=Nc3c(cnn3C)C(=O)N2c4ccc(cc4)CCO
  ACDLabs 12.01: O=C2c1cnn(c1N=C(N2c3ccc(CCO)cc3)SC(C)c4ccccc4)C
  OpenEye OEToolkits 2.0.7: CC(c1ccccc1)SC2=Nc3c(cnn3C)C(=O)N2c4ccc(cc4)CCO
  CACTVS 3.385: C[C@@H](SC1=Nc2n(C)ncc2C(=O)N1c3ccc(CCO)cc3)c4ccccc4
• Formula: C22 H22 N4 O2 S
• Name: 5-{4-[(Z)-2-hydroxyethenyl]phenyl}-1-methyl-6-{[(1R)-1-phenylethyl]sulfanyl}-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
• PDB chain: 7jww Chain A Residue 602

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7jww Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy.
• Resolution: 1.6 Å
• Binding residue (original residue number in PDB): G125 T129 F171 M175 Y297 C302 C303 I304 V460 F466
• Binding residue (residue number reindexed from 1): G118 T122 F164 M168 Y290 C295 C296 I297 V453 F459
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.36uM

Enzymatic activity

• Catalytic site (original residue number in PDB): N170 K193 E269 C303 E400 E477
• Catalytic site (residue number reindexed from 1): N163 K186 E262 C296 E393 E470
• Enzyme Commision number: 1.2.1.19: aminobutyraldehyde dehydrogenase.
  1.2.1.28: benzaldehyde dehydrogenase (NAD(+)).
  1.2.1.3: aldehyde dehydrogenase (NAD(+)).
  1.2.1.36: retinal dehydrogenase.

Gene Ontology

Molecular Function

• GO:0000166 nucleotide binding
• GO:0001758 retinal dehydrogenase activity
• GO:0004029 aldehyde dehydrogenase (NAD+) activity
• GO:0005096 GTPase activator activity
• GO:0005497 androgen binding
• GO:0005515 protein binding
• GO:0016491 oxidoreductase activity
• GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor
• GO:0018479 benzaldehyde dehydrogenase (NAD+) activity
• GO:0019145 aminobutyraldehyde dehydrogenase (NAD+) activity
• GO:0051287 NAD binding
• GO:0106373 3-deoxyglucosone dehydrogenase activity

Biological Process

• GO:0001523 retinoid metabolic process
• GO:0006081 cellular aldehyde metabolic process
• GO:0006629 lipid metabolic process
• GO:0009449 gamma-aminobutyric acid biosynthetic process
• GO:0030392 fructosamine catabolic process
• GO:0036438 maintenance of lens transparency
• GO:0042572 retinol metabolic process
• GO:0110095 cellular detoxification of aldehyde
• GO:0120163 negative regulation of cold-induced thermogenesis

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0030424 axon
• GO:0042995 cell projection
• GO:0045202 synapse
• GO:0070062 extracellular exosome

External links

• PDB: RCSB:7jww, PDBe:7jww, PDBj:7jww
• PDBsum: 7jww
• PubMed: 33341649
• UniProt: P00352|AL1A1_HUMAN Aldehyde dehydrogenase 1A1 (Gene Name=ALDH1A1)