Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.

• The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the "diffraction-before-destruction" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Strukturbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Structural Biology (hsv//eng)

Nyckelord

Amino Acid Sequence

Animals

Catalytic Domain

Cathepsin B

antagonists & inhibitors

chemistry

Crystallization

Crystallography

X-Ray

Enzyme Precursors

chemistry

Glycosylation

Models

Molecular

Molecular Sequence Data

Protein Conformation

Protozoan Proteins

antagonists & inhibitors

chemistry

Sf9 Cells

Spodoptera

Trypanosoma brucei brucei

enzymology

X-Rays

NATURAL SCIENCES

Publikations- och innehållstyp

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