AI Article Synopsis
- Ddi1 is a multidomain protein with a domain similar to retropepsin, which has been identified as a target for HIV-1 protease inhibitors.
- Crystal structure analysis revealed that Ddi1 forms a dimer and presents a distinct 'flap' region crucial for its functionality.
- Molecular dynamics simulations indicated that Ddi1 undergoes conformational changes, transitioning from open to semi-open and closed states as the flap covers the active site.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120238 | PMC |
| http://dx.doi.org/10.1002/2211-5463.12491 | DOI Listing |
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