Structure of PDB 6s4e Chain A Binding Site BS02

Receptor Information
>6s4e Chain A (length=292) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
MEAVVISGRKLAQQIKQEVRQEVEEWVASGNKRPHLSVILVGENPASHSY
VLNKTRAAAVVGINSETIMKPASISEEELLNLINKLNNDDNVDGLLVQLP
LPEHIDERRICNAVSPDKDVDGFHVINVGRMCLDQYSMLPATPWGVWEII
KRTGIPTLGKNVVVAGRSKNVGMPIAMLLHTDGAHERPGGDATVTISHRY
TPKEQLKKHTILADIVISAAGIPNLITADMIKEGAAVIDVGINRVHPKLV
GDVDFEGVRQKAGYITPVPGGVGPMTVAMLMKNTIIAAKKVL
Ligand information
Ligand IDNAD
InChIInChI=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
InChIKeyBAWFJGJZGIEFAR-NNYOXOHSSA-N
SMILES
SoftwareSMILES
CACTVS 3.341NC(=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 1.5.0c1cc(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 3.341NC(=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 1.5.0c1cc(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
FormulaC21 H27 N7 O14 P2
NameNICOTINAMIDE-ADENINE-DINUCLEOTIDE
ChEMBLCHEMBL1234613
DrugBankDB14128
ZINC
PDB chain6s4e Chain A Residue 406 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB6s4e Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.
Resolution1.9 Å
Binding residue
(original residue number in PDB)		R201 S202 N204 H232 R233 A253 A254 G255 I256 V274 G275 I276 T316
Binding residue
(residue number reindexed from 1)		R167 S168 N170 H198 R199 A219 A220 G221 I222 V240 G241 I242 T276
Annotation score4
Enzymatic activity
Catalytic site (original residue number in PDB) S81 K88 Q132 D155
Catalytic site (residue number reindexed from 1) S47 K54 Q98 D121
Enzyme Commision number 1.5.1.15: methylenetetrahydrofolate dehydrogenase (NAD(+)).
3.5.4.9: methenyltetrahydrofolate cyclohydrolase.
Gene Ontology
Molecular Function
GO:0000287 magnesium ion binding
GO:0003824 catalytic activity
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
GO:0004487 methylenetetrahydrofolate dehydrogenase (NAD+) activity
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
GO:0005515 protein binding
GO:0016491 oxidoreductase activity
GO:0016787 hydrolase activity
GO:0042301 phosphate ion binding
Biological Process
GO:0006730 one-carbon metabolic process
GO:0035999 tetrahydrofolate interconversion
GO:0046653 tetrahydrofolate metabolic process
GO:0046655 folic acid metabolic process
Cellular Component
GO:0005615 extracellular space
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:6s4e, PDBe:6s4e, PDBj:6s4e
PDBsum6s4e
PubMed35228749
UniProtP13995|MTDC_HUMAN Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (Gene Name=MTHFD2)

[Back to BioLiP]