Structure of PDB 4x4l Chain A Binding Site BS02

Receptor Information

>4x4l Chain A (length=493) Species: 9606 (Homo sapiens)

LPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKE
DVDKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMES
MNGGKLYSNAYLSDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHE
PIGVCGQIIPWNFPLVMLIWKIGPALSCGNTVVVKPAEQTPLTALHVASL
IKEAGFPPGVVNIVPGYGPTAGAAISSHMDIDKVAFTGSTEVGKLIKEAA
GKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQGQCCIAASR
IFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDLI
ESGKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQI
MKFKSLDDVIKRANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYG
VVSAQCPFGGFKMSGNGRELGEYGFHEYTEVKTVTVKISQKNS

Ligand information

• Ligand ID: NAI
• InChI: InChI=1S/C21H29N7O14P2/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(32)14(30)11(41-21)6-39-44(36,37)42-43(34,35)38-5-10-13(29)15(31)20(40-10)27-3-1-2-9(4-27)18(23)33/h1,3-4,7-8,10-11,13-16,20-21,29-32H,2,5-6H2,(H2,23,33)(H,34,35)(H,36,37)(H2,22,24,25)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
• InChIKey: BOPGDPNILDQYTO-NNYOXOHSSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OCC4C(C(C(O4)N5C=CCC(=C5)C(=O)N)O)O)O)O)N
  CACTVS 3.341: NC(=O)C1=CN(C=CC1)[C@@H]2O[C@H](CO[P@@](O)(=O)O[P@](O)(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]2O
  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)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)O)N
  CACTVS 3.341: NC(=O)C1=CN(C=CC1)[CH]2O[CH](CO[P](O)(=O)O[P](O)(=O)OC[CH]3O[CH]([CH](O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
• Formula: C21 H29 N7 O14 P2
• Name: 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE;
  NADH
• ChEMBL: CHEMBL1234616
• DrugBank: DB00157
• ZINC: ZINC000008215403
• PDB chain: 4x4l Chain A Residue 608

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4x4l Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors.
• Resolution: 1.85 Å
• Binding residue (original residue number in PDB): I166 I167 P168 W169 K193 E196 G226 G230 F244 T245 G246 S247 V250 C303 Q350 K353 E400 F402
• Binding residue (residue number reindexed from 1): I158 I159 P160 W161 K185 E188 G218 G222 F236 T237 G238 S239 V242 C295 Q342 K345 E392 F394
• Annotation score: 4

Enzymatic activity

• Catalytic site (original residue number in PDB): N170 K193 E269 C303 E400 E477
• Catalytic site (residue number reindexed from 1): N162 K185 E261 C295 E392 E469
• 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:4x4l, PDBe:4x4l, PDBj:4x4l
• PDBsum: 4x4l
• PubMed: 25634381
• UniProt: P00352|AL1A1_HUMAN Aldehyde dehydrogenase 1A1 (Gene Name=ALDH1A1)