Crystal structure of Trypanosoma brucei trypanothione reductase in complex with 1-(3,4-dichlorobenzyl)-4-(((5-((4-fluorophenethyl)carbamoyl)furan-2-yl)methyl)carbamoyl)-1-(3-phenylpropyl)piperazin-1-ium

Fragment Merging, Growing, and Linking Identify New Trypanothione Reductase Inhibitors for Leishmaniasis.

Due to flexibility of the N- and C-terminal parts, the electronic density was not well defined which prevent us from reconstructing the polypeptid chain.

N(1),N(8)-bis(glutathionyl)spermidine reductase

SHMSKAFDLVVIGAGSGGLEAGWNAATLYGKRVAVVDVQTSHGPPFYAALGGTCVNVGCVPKKLMVTGAQYMDHLRESAG
FGWEFDGSSVKANWKKLIAAKNEAVLDINKSYEGMFNDTEGLDFFLGWGSLESKNVVVVRETADPKSAVKERLQADHILL
ATGSWPQMPAIPGIEHCISSNEAFYLPEPPRRVLTVGGGFISVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREEV
TKQLTANGIEIMTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGNVGVKLTPKGGVQVDEFSRTN
VPNIYAIGDITDRLMLTPVAINEGAALVDTVFGNKPRKTDHTRVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFTP
LMHNISGSKYKKFVAKIVTNHSDGTVLGVHLLGDGAPEIIQAVGVCLRLNAKISDFYNTIGVHPTSAEELCSMRTPSYYY
VKGEKMEKLPDSNLD

SHMSKAFDLVVIGAGSGGLEAGWNAATLYGKRVAVVDVQTSHGPPFYAALGGTCVNVGCVPKKLMVTGAQYMDHLRESAG
FGWEFDGSSVKANWKKLIAAKNEAVLDINKSYEGMFNDTEGLDFFLGWGSLESKNVVVVRETADPKSAVKERLQADHILL
ATGSWPQMPAIPGIEHCISSNEAFYLPEPPRRVLTVGGGFISVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREEV
TKQLTANGIEIMTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGNVGVKLTPKGGVQVDEFSRTN
VPNIYAIGDITDRLMLTPVAINEGAALVDTVFGNKPRKTDHTRVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFTP
LMHNISGSKYKKFVAKIVTNHSDGTVLGVHLLGDGAPEIIQAVGVCLRLNAKISDFYNTIGVHPTSAEELCSMRTPSYYY
VKGEKMEKLPDSNL

GSHMSKAFDLVVIGAGSGGLEAGWNAATLYGKRVAVVDVQTSHGPPFYAALGGTCVNVGCVPKKLMVTGAQYMDHLRESA
GFGWEFDGSSVKANWKKLIAAKNEAVLDINKSYEGMFNDTEGLDFFLGWGSLESKNVVVVRETADPKSAVKERLQADHIL
LATGSWPQMPAIPGIEHCISSNEAFYLPEPPRRVLTVGGGFISVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREE
VTKQLTANGIEIMTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGNVGVKLTPKGGVQVDEFSRT
NVPNIYAIGDITDRLMLTPVAINEGAALVDTVFGNKPRKTDHTRVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFT
PLMHNISGSKYKKFVAKIVTNHSDGTVLGVHLLGDGAPEIIQAVGVCLRLNAKISDFYNTIGVHPTSAEELCSMRTPSYY
YVKGEKMEKLPDSNL

Structure of the same protein in complex with another inhibitor

The elution of the protein is compatible with that of a dimer of trypanothione reductase.
HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
oxidoreductase activity, nucleotide binding, flavoenzyme, inhibitor binding, OXIDOREDUCTASE

MSKAFDLVVIGAGSGGLEAGWNAATLYGKRVAVVDVQTSHGPPFYAALGGTCVNVGCVPKKLMVTGAQYMDHLRESAGFG
WEFDGSSVKANWKKLIAAKNEAVLDINKSYEGMFNDTEGLDFFLGWGSLESKNVVVVRETADPKSAVKERLQADHILLAT
GSWPQMPAIPGIEHCISSNEAFYLPEPPRRVLTVGGGFISVEFAGIFNAYKPPGGKVTLCYRNNLILRGFDETIREEVTK
QLTANGIEIMTNENPAKVSLNTDGSKHVTFESGKTLDVDVVMMAIGRIPRTNDLQLGNVGVKLTPKGGVQVDEFSRTNVP
NIYAIGDITDRLMLTPVAINEGAALVDTVFGNKPRKTDHTRVASAVFSIPPIGTCGLIEEVAAKEFEKVAVYMSSFTPLM
HNISGSKYKKFVAKIVTNHSDGTVLGVHLLGDGAPEIIQAVGVCLRLNAKISDFYNTIGVHPTSAEELCSMRTPSYYYVK
GEKMEKLPDSNL