Structure of PDB 7x12 Chain B Binding Site BS02

Receptor Information

>7x12 Chain B (length=564) Species: 9606 (Homo sapiens)

PRRRHTHQRGYLLTRNPHLNKDLAFTLEERQQLNIHGLLPPSFNSQEIQV
LRVVKNFEHLNSDFDRYLLLMDLQDRNEKLFYRVLTSDIEKFMPIVYTPT
VGLACQQYSLVFRKPRGLFITIHDRGHIASVLNAWPEDVIKAIVVTDGER
ILGLGDLGCNGMGIPVGKLALYTACGGMNPQECLPVILDVGTENEELLKD
PLYIGLRQRRVRGSEYDDFLDEFMEAVSSKYGMNCLIQFEDFANVNAFRL
LNKYRNQYCTFNDDIQGTASVAVAGLLAALRITKNKLSDQTILFQGAGEA
ALGIAHLIVMALEKEGLPKEKAIKKIWLVDSKGLIVKGRASLTQEKEKFA
HEHEEMKNLEAIVQEIKPTALIGVAAIGGAFSEQILKDMAAFNERPIIFA
LSNPTSKAECSAEQCYKITKGRAIFASGSPFDPVTLPNGQTLYPGQGNNS
YVFPGVALGVVACGLRQITDNIFLTTAEVIAQQVSDKHLEEGRLYPPLNT
IRDVSLKIAEKIVKDAYQEKTATVYPEPQNKEAFVRSQMYSTDYDQILPD
CYSWPEEVQKIQTK

Ligand information

• Ligand ID: NDP
• InChI: InChI=1S/C21H30N7O17P3/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/h1,3-4,7-8,10-11,13-16,20-21,29-31H,2,5-6H2,(H2,23,32)(H,36,37)(H,38,39)(H2,22,24,25)(H2,33,34,35)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
• InChIKey: ACFIXJIJDZMPPO-NNYOXOHSSA-N
• SMILES:
  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)OP(=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[P](O)(O)=O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
  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[P](O)(O)=O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]2O
  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)OP(=O)(O)O)N
• Formula: C21 H30 N7 O17 P3
• Name: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
• ChEMBL: CHEMBL407009
• DrugBank: DB02338
• ZINC: ZINC000008215411
• PDB chain: 7x12 Chain B Residue 602

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7x12 Discovery and Characterization of a Novel Allosteric Small-Molecule Inhibitor of NADP + -Dependent Malic Enzyme 1.
• Resolution: 2.07 Å
• Binding residue (original residue number in PDB): T283 Q310 A312 G313 E314 A315 V344 D345 S346 K361 V389 A390 I392 L416 S417 N418 G462
• Binding residue (residue number reindexed from 1): T268 Q295 A297 G298 E299 A300 V329 D330 S331 K346 V374 A375 I377 L401 S402 N403 G447
• Annotation score: 4

Enzymatic activity

• Enzyme Commision number: 1.1.1.40: malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+)).

Gene Ontology

Molecular Function

• GO:0000287 magnesium ion binding
• GO:0004470 malic enzyme activity
• GO:0004473 malate dehydrogenase (decarboxylating) (NADP+) activity
• GO:0005515 protein binding
• GO:0008948 oxaloacetate decarboxylase activity
• GO:0009055 electron transfer activity
• GO:0016491 oxidoreductase activity
• GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
• GO:0030145 manganese ion binding
• GO:0042802 identical protein binding
• GO:0043531 ADP binding
• GO:0046872 metal ion binding
• GO:0050661 NADP binding
• GO:0051287 NAD binding

Biological Process

• GO:0005975 carbohydrate metabolic process
• GO:0006090 pyruvate metabolic process
• GO:0006108 malate metabolic process
• GO:0006734 NADH metabolic process
• GO:0006739 NADP metabolic process
• GO:0009165 nucleotide biosynthetic process
• GO:0009725 response to hormone
• GO:0009743 response to carbohydrate
• GO:0051289 protein homotetramerization
• GO:1902031 regulation of NADP metabolic process

Cellular Component

• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005829 cytosol

External links

• PDB: RCSB:7x12, PDBe:7x12, PDBj:7x12
• PDBsum: 7x12
• PubMed: 35819845
• UniProt: P48163|MAOX_HUMAN NADP-dependent malic enzyme (Gene Name=ME1)