3f75

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Activated Toxoplasma gondii cathepsin L (TgCPL) in complex with its propeptideActivated Toxoplasma gondii cathepsin L (TgCPL) in complex with its propeptide

Structural highlights

3f75 is a 2 chain structure with sequence from Toxoplasma gondii RH. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.99Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q6DMN0_TOXGO

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The protozoan parasite Toxoplasma gondii relies on post-translational modification, including proteolysis, of proteins required for recognition and invasion of host cells. We have characterized the T. gondii cysteine protease cathepsin L (TgCPL), one of five cathepsins found in the T. gondii genome. We show that TgCPL is the primary target of the compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl (LHVS), which was previously shown to inhibit parasite invasion by blocking the release of invasion proteins from microneme secretory organelles. As shown by fluorescently labeled LHVS and TgCPL-specific antibodies, TgCPL is associated with a discrete vesicular structure in the apical region of extracellular parasites but is found in multiple puncta throughout the cytoplasm of intracellular replicating parasites. LHVS fails to label cells lacking TgCPL due to targeted disruption of the TgCPL gene in two different parasite strains. We present a structural model for the inhibition of TgCPL by LHVS based on a 2.0 A resolution crystal structure of TgCPL in complex with its propeptide. We discuss possible roles for TgCPL as a protease involved in the degradation or limited proteolysis of parasite proteins involved in invasion.

Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl.,Larson ET, Parussini F, Huynh MH, Giebel JD, Kelley AM, Zhang L, Bogyo M, Merritt EA, Carruthers VB J Biol Chem. 2009 Sep 25;284(39):26839-50. Epub 2009 Jul 13. PMID:19596863[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Larson ET, Parussini F, Huynh MH, Giebel JD, Kelley AM, Zhang L, Bogyo M, Merritt EA, Carruthers VB. Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl. J Biol Chem. 2009 Sep 25;284(39):26839-50. Epub 2009 Jul 13. PMID:19596863 doi:10.1074/jbc.M109.003780

3f75, resolution 1.99Å

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OCA