2b7f
From Proteopedia
Crystal structure of human T-cell leukemia virus protease, a novel target for anti-cancer design
Structural highlights
Function[PRO_HTL1A] Matrix protein p19 targets Gag, Gag-Pro and Gag-Pro-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex (By similarity). Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p15 is involved in the packaging and encapsidation of two copies of the genome. The aspartyl protease mediates proteolytic cleavages of Gag, Gag-Pro and Gag-Pro-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Hydrolyzes host EIF4GI in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design.,Li M, Laco GS, Jaskolski M, Rozycki J, Alexandratos J, Wlodawer A, Gustchina A Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18332-7. Epub 2005 Dec 13. PMID:16352712[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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