Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein.

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 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.

journal_name

FEBS Open Bio

journal_title

FEBS open bio

authors

Kumar S,Suguna K

doi

10.1002/2211-5463.12491

subject

Has Abstract

pub_date

2018-08-03 00:00:00

pages

1379-1394

issue

9

issn

2211-5463

pii

FEB412491

journal_volume

8

pub_type

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