2B7F

Crystal structure of human T-cell leukemia virus protease, a novel target for anti-cancer design

Summary for 2B7F

• Entry DOI: 10.2210/pdb2b7f/pdb
• Related PRD ID: PRD_000429
• Descriptor: HTLV protease, (ACE)APQV(STA)VMHP peptide, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human T-lymphotropic virus 1
• Cellular location: Matrix protein p19: Virion . Capsid protein p24: Virion . Nucleocapsid protein p15-pro: Virion : P10274
• Total number of polymer chains: 9
• Total formula weight: 78776.32

Authors

Li, M.,Laco, G.S.,Jaskolski, M.,Rozycki, J.,Alexandratos, J.,Wlodawer, A.,Gustchina, A. (deposition date: 2005-10-04, release date: 2005-12-06, Last modification date: 2024-10-09)

Primary citation

Li, M.,Laco, G.S.,Jaskolski, M.,Rozycki, J.,Alexandratos, J.,Wlodawer, A.,Gustchina, A.
Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design
Proc.Natl.Acad.Sci.Usa, 102:18332-18337, 2005

PubMed Abstract: The successful development of a number of HIV-1 protease (PR) inhibitors for the treatment of AIDS has validated the utilization of retroviral PRs as drug targets and necessitated their detailed structural study. Here we report the structure of a complex of human T cell leukemia virus type 1 (HTLV-1) PR with a substrate-based inhibitor bound in subsites P5 through P5'. Although HTLV-1 PR exhibits an overall fold similar to other retroviral PRs, significant structural differences are present in several loop areas, which include the functionally important flaps, previously considered to be structurally highly conserved. Potential key residues responsible for the resistance of HTLV-1 PR to anti-HIV drugs are identified. We expect that the knowledge accumulated during the development of anti-HIV drugs, particularly in overcoming drug resistance, will help in designing a novel class of antileukemia drugs targeting HTLV-1 PR and in predicting their drug-resistance profile. The structure presented here can be used as a starting point for the development of such anticancer therapies.

PubMed: 16352712
DOI: 10.1073/pnas.0509335102

Experimental method

X-RAY DIFFRACTION (2.6 Å)