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![[Figure 5]](rr5143fig5mag.jpg)
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Figure 5
Cryo-EM structure of the P. falciparum 20S proteasome with an inhibitor bound, showing the map and coordinates deposited in the Electron Microscopy Data Bank and Protein Data Bank with accession codes EMD-3231 and 5fmg, respectively (Li, O'Donoghue et al., 2016  ). (a) Overall view of the density map (mesh) and protein coordinates (cartoon). (b) Close-up view of the density map (mesh) and model coordinates (sticks) showing the WLW-vs inhibitor (teal) bound to Thr1 of the β2 subunit. The ligand WLW tripeptide mimics proteasome substrate positions P1–P3, as labelled. As for other tripeptide proteasome inhibitors, the side chains at positions P1 and P3 are oriented towards the ligand-binding pocket, while that at position P2 is oriented towards the inner cavity of the proteasome. (c) Model of the P. falciparum β2 active site with bound ligand, as determined by cryo-EM, viewed towards the inner cavity of the proteasome. (d) P. falciparum β1 active site with superimposed inhibitor coordinates, showing that the tryptophan side chains of the ligand, at positions P1 and P3, cannot be accommodated at this active site owing to steric constraints. (e) P. falciparum β5 active site with superimposed inhibitor coordinates, showing that the tryptophan side chain of the ligand at position P1 cannot be accommodated in this active site owing to steric constraints. In (c), (d) and (e) the protein model is represented as van der Waals surfaces and the ligand as sticks. (a), (c), (d) and (e) were created using UCSF Chimera (Pettersen et al., 2004) and (b) was created using PyMOL (Schrödinger). |
![[Figure 5]](rr5143fig5.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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