Open AccessCrystal structure of the retroviral protease‐like domain of a protozoal DNA damage‐inducible 1 protein
Author(s) -
Kumar Sushant,
Suguna Kaza
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12491
Subject(s) - protease , docking (animal) , leishmania , microbiology and biotechnology , dna , dimer , chemistry , biology , leishmania major , biochemistry , enzyme , parasite hosting , medicine , nursing , organic chemistry , world wide web , computer science
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 Leishmania and Plasmodium , and some of them were shown to inhibit the growth of these parasites. In Leishmania , Ddi1 was identified as a likely target of the inhibitors. We report the crystal structure of the retropepsin‐like domain of Ddi1 from Leishmania major 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.