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

Kumar, Sushant and Suguna, Kaza (2018) Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein. In: FEBS OPEN BIO, 8 (9). pp. 1379-1394.

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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.

Item Type:	Journal Article
Publication:	FEBS OPEN BIO
Publisher:	WILEY
Additional Information:	Copy right for this article belong to WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords:	crystal structure; Ddi1; DNA damage-inducible 1 protein; Leishmania major; saquinavir
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	24 Sep 2018 15:38
Last Modified:	24 Sep 2018 15:38
URI:	http://eprints.iisc.ac.in/id/eprint/60687

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