Structure of PDB 2wpe Chain A Binding Site BS01

Receptor Information

>2wpe Chain A (length=490) Species: 185431 (Trypanosoma brucei brucei TREU927)

SHMSKAFDLVVIGAGSGGLEAGWNAATLYGKRVAVVDVQTSHGPPFYAAL
GGTCVNVGCVPKKLMVTGAQYMDHLRESAGFGWEFDGSSVKANWKKLIAA
KNEAVLDINKSYEGMFNDTEGLDFFLGWGSLESKNVVVVRETADPKSAVK
ERLQADHILLATGSWPQMPAIPGIEHCISSNEAFYLPEPPRRVLTVGGGF
ISVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREEVTKQLTANGIE
IMTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGN
VGVKLTPKGGVQVDEFSRTNVPNIYAIGDITDRLMLTPVAINEGAALVDT
VFGNKPRKTDHTRVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFTP
LMHNISGSKYKKFVAKIVTNHSDGTVLGVHLLGDGAPEIIQAVGVCLRLN
AKISDFYNTIGVHPTSAEELCSMRTPSYYYVKGEKMEKLP

Ligand information

• Ligand ID: FAD
• InChI: InChI=1S/C27H33N9O15P2/c1-10-3-12-13(4-11(10)2)35(24-18(32-12)25(42)34-27(43)33-24)5-14(37)19(39)15(38)6-48-52(44,45)51-53(46,47)49-7-16-20(40)21(41)26(50-16)36-9-31-17-22(28)29-8-30-23(17)36/h3-4,8-9,14-16,19-21,26,37-41H,5-7H2,1-2H3,(H,44,45)(H,46,47)(H2,28,29,30)(H,34,42,43)/t14-,15+,16+,19-,20+,21+,26+/m0/s1
• InChIKey: VWWQXMAJTJZDQX-UYBVJOGSSA-N
• SMILES:
  CACTVS 3.341: Cc1cc2N=C3C(=O)NC(=O)N=C3N(C[C@H](O)[C@H](O)[C@H](O)CO[P@](O)(=O)O[P@@](O)(=O)OC[C@H]4O[C@H]([C@H](O)[C@@H]4O)n5cnc6c(N)ncnc56)c2cc1C
  OpenEye OEToolkits 1.5.0: Cc1cc2c(cc1C)N(C3=NC(=O)NC(=O)C3=N2)CC(C(C(COP(=O)(O)OP(=O)(O)OCC4C(C(C(O4)n5cnc6c5ncnc6N)O)O)O)O)O
  OpenEye OEToolkits 1.5.0: Cc1cc2c(cc1C)N(C3=NC(=O)NC(=O)C3=N2)C[C@@H]([C@@H]([C@@H](CO[P@@](=O)(O)O[P@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)n5cnc6c5ncnc6N)O)O)O)O)O
  CACTVS 3.341: Cc1cc2N=C3C(=O)NC(=O)N=C3N(C[CH](O)[CH](O)[CH](O)CO[P](O)(=O)O[P](O)(=O)OC[CH]4O[CH]([CH](O)[CH]4O)n5cnc6c(N)ncnc56)c2cc1C
  ACDLabs 10.04: O=C2C3=Nc1cc(c(cc1N(C3=NC(=O)N2)CC(O)C(O)C(O)COP(=O)(O)OP(=O)(O)OCC6OC(n5cnc4c(ncnc45)N)C(O)C6O)C)C
• Formula: C27 H33 N9 O15 P2
• Name: FLAVIN-ADENINE DINUCLEOTIDE
• ChEMBL: CHEMBL1232653
• DrugBank: DB03147
• ZINC: ZINC000008215434
• PDB chain: 2wpe Chain A Residue 998

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2wpe Dihydroquinazolines as a Novel Class of Trypanosoma Brucei Trypanothione Reductase Inhibitors: Discovery, Synthesis, and Characterization of Their Binding Mode by Protein Crystallography.
• Resolution: 2.1 Å
• Binding residue (original residue number in PDB): I10 G11 G13 S14 G15 V34 D35 V36 A46 A47 G50 T51 C52 G56 C57 K60 W126 G127 T160 G161 F198 R287 R290 G326 D327 M333 L334 T335
• Binding residue (residue number reindexed from 1): I12 G13 G15 S16 G17 V36 D37 V38 A48 A49 G52 T53 C54 G58 C59 K62 W128 G129 T162 G163 F200 R289 R292 G328 D329 M335 L336 T337
• Annotation score: 2

Enzymatic activity

• Catalytic site (original residue number in PDB): S14 L48 C52 C57 K60 G85 S86 F198 E202 I339 G459 H461 E466 E485 K486
• Catalytic site (residue number reindexed from 1): S16 L50 C54 C59 K62 G87 S88 F200 E204 I341 G461 H463 E468 E487 K488
• Enzyme Commision number: 1.8.1.12: trypanothione-disulfide reductase.

Gene Ontology

Molecular Function

• GO:0000166 nucleotide binding
• GO:0004791 thioredoxin-disulfide reductase (NADPH) activity
• GO:0015036 disulfide oxidoreductase activity
• GO:0015042 trypanothione-disulfide reductase (NADPH) activity
• GO:0016491 oxidoreductase activity
• GO:0016668 oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor
• GO:0046872 metal ion binding
• GO:0050660 flavin adenine dinucleotide binding

Biological Process

• GO:0045454 cell redox homeostasis
• GO:0098869 cellular oxidant detoxification

Cellular Component

• GO:0005654 nucleoplasm
• GO:0005737 cytoplasm
• GO:0020015 glycosome
• GO:0097014 ciliary plasm

External links

• PDB: RCSB:2wpe, PDBe:2wpe, PDBj:2wpe
• PDBsum: 2wpe
• PubMed: 21851087
• UniProt: Q389T8