5YS4

Crystal structure of retroviral protease-like domain of Ddi1 from Leishmania major

Summary for 5YS4

• Entry DOI: 10.2210/pdb5ys4/pdb
• Descriptor: DNA-damage inducible protein DDI1-like protein (2 entities in total)
• Functional Keywords: retropepsin, aspartic protease, cytoplasmic, hydrolase
• Biological source: Leishmania major
• Total number of polymer chains: 6
• Total formula weight: 87565.61

Authors

Suguna, K.,Kumar, S. (deposition date: 2017-11-13, release date: 2018-11-21, Last modification date: 2023-11-22)

Primary citation

Kumar, S.,Suguna, K.
Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein.
FEBS Open Bio, 8:1379-1394, 2018

PubMed Abstract: DNA damage-inducible 1 (Ddi1) is a multidomain protein with one of the domains being retropepsin-like. HIV-1 protease inhibitors were found to reduce opportunistic infections caused by pathogens like and , and some of them were shown to inhibit the growth of these parasites. In , Ddi1 was identified as a likely target of the inhibitors. We report the crystal structure of the retropepsin-like domain of Ddi1 from as a dimer with clear density for the critical 'flap' region. We have characterized binding with one of the HIV-1 protease inhibitors in solution using bio-layer interferometry and by docking. Further, we have performed molecular dynamics (MD) simulation studies that show that the protein undergoes a conformational change from open to semi-open and closed forms with the closing of the flexible flap over the active site.

PubMed: 30186740
DOI: 10.1002/2211-5463.12491

Experimental method

X-RAY DIFFRACTION (2.3 Å)