Structure of PDB 1dib Chain B Binding Site BS01

Receptor Information

>1dib Chain B (length=295) Species: 9606 (Homo sapiens)

APAEILNGKEISAQIRARLKNQVTQLKEQVPGFTPRLAILQVGNRDDSNL
YINVKLKAAEEIGIKATHIKLPRTTTESEVMKYITSLNEDSTVHGFLVQL
PLDSENSINTEEVINAIAPEKDVDGLTSINAGRLARGDLNDCFIPCTPKG
CLELIKETGVPIAGRHAVVVGRSKIVGAPMHDLLLWNNATVTTCHSKTAH
LDEEVNKGDILVVATGQPEMVKGEWIKPGAIVIDCGINYVPDDKKPNGRK
VVGDVAYDEAKERASFITPVPGGVGPMTVAMLMQSTVESAKRFLE

Ligand information

• Ligand ID: NAP
• InChI: InChI=1S/C21H28N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1-4,7-8,10-11,13-16,20-21,29-31H,5-6H2,(H7-,22,23,24,25,32,33,34,35,36,37,38,39)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
• InChIKey: XJLXINKUBYWONI-NNYOXOHSSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1cc(c[n+](c1)C2C(C(C(O2)COP(=O)([O-])OP(=O)(O)OCC3C(C(C(O3)n4cnc5c4ncnc5N)OP(=O)(O)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[P](O)(O)=O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
  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[P](O)(O)=O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]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)OP(=O)(O)O)O)O)O)C(=O)N
• Formula: C21 H28 N7 O17 P3
• Name: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE;
  2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE
• ChEMBL: CHEMBL295069
• DrugBank: DB03461
• PDB chain: 1dib Chain B Residue 2002

Receptor-Ligand Complex Structure

Structure summary

• PDB: 1dib Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase.
• Resolution: 2.7 Å
• Binding residue (original residue number in PDB): T1148 G1172 R1173 S1174 H1196 S1197 L1202 T1216 Q1218 M1221 C1236 I1238
• Binding residue (residue number reindexed from 1): T147 G171 R172 S173 H195 S196 L201 T215 Q217 M220 C235 I237
• Annotation score: 4

Enzymatic activity

• Catalytic site (original residue number in PDB): S1049 K1056 Q1100 D1125
• Catalytic site (residue number reindexed from 1): S48 K55 Q99 D124
• Enzyme Commision number: 1.5.1.5: methylenetetrahydrofolate dehydrogenase (NADP(+)).
  3.5.4.9: methenyltetrahydrofolate cyclohydrolase.
  6.3.4.3: formate--tetrahydrofolate ligase.

Gene Ontology

Molecular Function

• GO:0003824 catalytic activity
• GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity

External links

• PDB: RCSB:1dib, PDBe:1dib, PDBj:1dib
• PDBsum: 1dib
• PubMed: 10828945
• UniProt: P11586|C1TC_HUMAN C-1-tetrahydrofolate synthase, cytoplasmic (Gene Name=MTHFD1)