3LIT

The crystal structure of htlv protease complexed with the inhibitor KNI-10681

Summary for 3LIT

• Entry DOI: 10.2210/pdb3lit/pdb
• Related: 2B7F 3LIN 3LIQ 3LIV 3LIX 3LIY
• Related PRD ID: PRD_000579
• Descriptor: Protease, (4R)-3-[(2S,3S)-3-[[(2S)-2-[[(2S)-2-azanyl-2-phenyl-ethanoyl]amino]-3,3-dimethyl-butanoyl]amino]-2-hydroxy-4-phenyl-but anoyl]-5,5-dimethyl-N-[(2R)-3-methylbutan-2-yl]-1,3-thiazolidine-4-carboxamide (3 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human T-lymphotropic virus 1
• Total number of polymer chains: 2
• Total formula weight: 25787.03

Authors

Satoh, T.,Li, M.,Nguyen, J.,Kiso, Y.,Wlodawer, A.,Gustchina, A. (deposition date: 2010-01-25, release date: 2010-07-14, Last modification date: 2023-09-06)

Primary citation

Satoh, T.,Li, M.,Nguyen, J.T.,Kiso, Y.,Gustchina, A.,Wlodawer, A.
Crystal structures of inhibitor complexes of human T-cell leukemia virus (HTLV-1) protease.
J.Mol.Biol., 401:626-641, 2010

PubMed Abstract: Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailed study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.

PubMed: 20600105
DOI: 10.1016/j.jmb.2010.06.052

Experimental method

X-RAY DIFFRACTION (2.19 Å)