Structure of PDB 7a6q Chain A Binding Site BS01

Receptor Information

>7a6q Chain A (length=489) Species: 9606 (Homo sapiens)

ALPRPIRNLEVKFTKIFINNEWHESKSGKKFATCNPSTREQICEVEEGDK
PDVDKAVEAAQVAFQRGSPWRRLDALSRGRLLHQLADLVERDRATLAALE
TMDTGKPFLHAFFIDLEGCIRTLRYFAGWADKIQGKTIPTDDNVVCFTRH
EPIGVCGAITPWNFPLLMLVWKLAPALCCGNTMVLKPAEQTPLTALYLGS
LIKEAGFPPGVVNIVPGFGPTVGAAISSHPQINKIAFTGSTEVGKLVKEA
ASRSNLKRVTLELGGKNPCIVCADADLDLAVECAHQGVFFNQGQCCTAAS
RVFVEEQVYSEFVRRSVEYAKKRPVGDPFDVKTEQGPQIDQKQFDKILEL
IESGKKEGAKLECGGSAMEDKGLFIKPTVFSEVTDNMRIAKEEIFGPVQP
ILKFKSIEEVIKRANSTDYGLTAAVFTKNLDKALKLASALESGTVWINCY
NALYAQAPFGGFKMSGNGRELGEYALAEYTEVKTVTIKL

Ligand information

• Ligand ID: NAD
• InChI: InChI=1S/C21H27N7O14P2/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/h1-4,7-8,10-11,13-16,20-21,29-32H,5-6H2,(H5-,22,23,24,25,33,34,35,36,37)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
• InChIKey: BAWFJGJZGIEFAR-NNYOXOHSSA-N
• SMILES:
  CACTVS 3.341: NC(=O)c1ccc[n+](c1)[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: c1cc(c[n+](c1)C2C(C(C(O2)COP(=O)([O-])OP(=O)(O)OCC3C(C(C(O3)n4cnc5c4ncnc5N)O)O)O)O)C(=O)N
  CACTVS 3.341: NC(=O)c1ccc[n+](c1)[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
  OpenEye OEToolkits 1.5.0: c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)O)O)O)O)C(=O)N
• Formula: C21 H27 N7 O14 P2
• Name: NICOTINAMIDE-ADENINE-DINUCLEOTIDE
• ChEMBL: CHEMBL1234613
• DrugBank: DB14128
• PDB chain: 7a6q Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7a6q A Selective Competitive Inhibitor of Aldehyde Dehydrogenase 1A3 Hinders Cancer Cell Growth, Invasiveness and Stemness In Vitro.
• Resolution: 2.95 Å
• Binding residue (original residue number in PDB): I177 T178 W180 K204 A206 E207 G237 G241 S258 V261 K360 K364
• Binding residue (residue number reindexed from 1): I159 T160 W162 K186 A188 E189 G219 G223 S240 V243 K342 K346
• Annotation score: 4

Enzymatic activity

• Catalytic site (original residue number in PDB): N181 E280 C314 E488
• Catalytic site (residue number reindexed from 1): N163 E262 C296 E470
• Enzyme Commision number: 1.2.1.36: retinal dehydrogenase.

Gene Ontology

Molecular Function

• GO:0001758 retinal dehydrogenase activity
• GO:0004029 aldehyde dehydrogenase (NAD+) activity
• GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity
• GO:0016491 oxidoreductase activity
• GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor
• GO:0042803 protein homodimerization activity
• GO:0070324 thyroid hormone binding
• GO:0070403 NAD+ binding

Biological Process

• GO:0002072 optic cup morphogenesis involved in camera-type eye development
• GO:0002138 retinoic acid biosynthetic process
• GO:0006629 lipid metabolic process
• GO:0006915 apoptotic process
• GO:0007626 locomotory behavior
• GO:0021768 nucleus accumbens development
• GO:0031076 embryonic camera-type eye development
• GO:0042472 inner ear morphogenesis
• GO:0042572 retinol metabolic process
• GO:0042573 retinoic acid metabolic process
• GO:0042574 retinal metabolic process
• GO:0043065 positive regulation of apoptotic process
• GO:0043584 nose development
• GO:0048048 embryonic eye morphogenesis
• GO:0050885 neuromuscular process controlling balance
• GO:0051289 protein homotetramerization
• GO:0060013 righting reflex
• GO:0060166 olfactory pit development
• GO:0060324 face development
• GO:0070384 Harderian gland development

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome

External links

• PDB: RCSB:7a6q, PDBe:7a6q, PDBj:7a6q
• PDBsum: 7a6q
• PubMed: 33478031
• UniProt: P47895|AL1A3_HUMAN Retinaldehyde dehydrogenase 3 (Gene Name=ALDH1A3)