4CKU: Three dimensional structure of plasmepsin II in complex with hydroxyethylamine-based inhibitor

Antimalarial hit 1 SR (TCMDC-134674) identified in a GlaxoSmithKline cell based screening campaign was evaluated for inhibitory activity against the digestive vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1 SR bound to Plm II was solved, providing structural insight for the design of more potent and selective analogues. Structure-guided optimization led to the identification of structurally simplified analogues 17 and 18 as low nanomolar inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in erythrocytes.
PDB ID: 4CKUDownload
MMDB ID: 120745
PDB Deposition Date: 2014/1/8
Updated in MMDB: 2014/06
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 4CKU: tetrameric; determined by author and by software (PISA)
Molecular Components in 4CKU
Label Count Molecule
Proteins (4 molecules)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB