Structure of PDB 6rb5 Chain B Binding Site BS03

Receptor Information
>6rb5 Chain B (length=489) Species: 5691 (Trypanosoma brucei) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
HMSKAFDLVVIGAGSGGLEAGWNAATLYGKRVAVVDVQTSHGPPFYAALG
GTCVNVGCVPKKLMVTGAQYMDHLRESAGFGWEFDGSSVKANWKKLIAAK
NEAVLDINKSYEGMFNDTEGLDFFLGWGSLESKNVVVVRETADPKSAVKE
RLQADHILLATGSWPQMPAIPGIEHCISSNEAFYLPEPPRRVLTVGGGFI
SVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREEVTKQLTANGIEI
MTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGNV
GVKLTPKGGVQVDEFSRTNVPNIYAIGDITDRLMLTPVAINEGAALVDTV
FGNKPRKTDHTRVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFTPL
MHNISGSKYKKFVAKIVTNHSDGTVLGVHLLGDGAPEIIQAVGVCLRLNA
KISDFYNTIGVHPTSAEELCSMRTPSYYYVKGEKMEKLP
Ligand information
Ligand IDJWZ
InChIInChI=1S/C35H57N7O2/c1-33(2)28-11-10-27(30(33)24-28)12-19-39-20-15-35(16-21-39)31(43)41(26-42(35)29-8-5-4-6-9-29)18-7-17-38(3)25-34(44)13-22-40(23-14-34)32(36)37/h4-6,8-9,27-28,30,44H,7,10-26H2,1-3H3,(H3,36,37)/t27-,28-,30-/m0/s1
InChIKeyBOKDSYBHRKGRCS-XEVVZDEMSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CN(CCCN1CN(c2ccccc2)[C@]3(CCN(CC[C@@H]4CC[C@H]5C[C@@H]4C5(C)C)CC3)C1=O)CC6(O)CCN(CC6)C(N)=N
CACTVS 3.385CN(CCCN1CN(c2ccccc2)[C]3(CCN(CC[CH]4CC[CH]5C[CH]4C5(C)C)CC3)C1=O)CC6(O)CCN(CC6)C(N)=N
OpenEye OEToolkits 2.0.7[H]/N=C(/N)\N1CCC(CC1)(CN(C)CCCN2CN(C3(C2=O)CCN(CC3)CC[C@@H]4CC[C@H]5C[C@@H]4C5(C)C)c6ccccc6)O
OpenEye OEToolkits 2.0.7CC1(C2CCC(C1C2)CCN3CCC4(CC3)C(=O)N(CN4c5ccccc5)CCCN(C)CC6(CCN(CC6)C(=N)N)O)C
FormulaC35 H57 N7 O2
Name4-(((3-(8-(2-((1R,2S,5R)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)propyl)(methyl)amino)methyl)-4-hydroxypiperidine-1-carboximidamide
ChEMBL
DrugBank
ZINC
PDB chain6rb5 Chain B Residue 507 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB6rb5 Spiro-containing derivatives show antiparasitic activity against Trypanosoma brucei through inhibition of the trypanothione reductase enzyme.
Resolution1.977 Å
Binding residue
(original residue number in PDB)		S86 V88 K89 P213
Binding residue
(residue number reindexed from 1)		S87 V89 K90 P214
Annotation score1
Binding affinityMOAD: ic50=3.5uM
Enzymatic activity
Catalytic site (original residue number in PDB) C52 C57 K60 F198 E202 H461 E466 E485 K486
Catalytic site (residue number reindexed from 1) C53 C58 K61 F199 E203 H462 E467 E486 K487
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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:6rb5, PDBe:6rb5, PDBj:6rb5
PDBsum6rb5
PubMed32437349
UniProtQ389T8

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