2b7f
From Proteopedia
(New page: 200px<br /><applet load="2b7f" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b7f, resolution 2.60Å" /> '''Crystal structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2b7f.gif|left|200px]]<br /><applet load="2b7f" size=" | + | [[Image:2b7f.gif|left|200px]]<br /><applet load="2b7f" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2b7f, resolution 2.60Å" /> | caption="2b7f, resolution 2.60Å" /> | ||
'''Crystal structure of human T-cell leukemia virus protease, a novel target for anti-cancer design'''<br /> | '''Crystal structure of human T-cell leukemia virus protease, a novel target for anti-cancer design'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The successful development of a number of HIV-1 protease (PR) inhibitors | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2B7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_t-cell_leukemia_virus_type_i Human t-cell leukemia virus type i] with PO4 and ACE as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2B7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_t-cell_leukemia_virus_type_i Human t-cell leukemia virus type i] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B7F OCA]. |
==Reference== | ==Reference== | ||
| Line 16: | Line 16: | ||
[[Category: Gustchina, A.]] | [[Category: Gustchina, A.]] | ||
[[Category: Jaskolski, M.]] | [[Category: Jaskolski, M.]] | ||
| - | [[Category: Laco, G | + | [[Category: Laco, G S.]] |
[[Category: Li, M.]] | [[Category: Li, M.]] | ||
[[Category: Rozycki, J.]] | [[Category: Rozycki, J.]] | ||
| Line 24: | Line 24: | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:34:54 2008'' |
Revision as of 14:34, 21 February 2008
|
Crystal structure of human T-cell leukemia virus protease, a novel target for anti-cancer design
Overview
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.
About this Structure
2B7F is a Single protein structure of sequence from Human t-cell leukemia virus type i with and as ligands. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:34:54 2008
