人 T 细胞白血病病毒（HTLV-1）蛋白酶抑制剂复合物的晶体结构。
Crystal structures of inhibitor complexes of human T-cell leukemia virus (HTLV-1) protease.
机构信息
Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
出版信息
J Mol Biol. 2010 Aug 27;401(4):626-41. doi: 10.1016/j.jmb.2010.06.052. Epub 2010 Jun 30.
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.
摘要
人类 T 细胞白血病病毒 1 型（HTLV-1）是一种逆转录病毒，与几种严重疾病相关，如成人 T 细胞白血病和热带痉挛性截瘫/脊髓病。多年来，HTLV-1 编码的蛋白酶（PR）一直是设计抗病毒药物的目标，但由于可用的结构信息有限，这一努力受到了阻碍。我们报告了 HTLV-1 PR 与含司他汀抑制剂复合物的高分辨率晶体结构，这比以前可用的中分辨率结构有了显著改善。我们还报告了 HTLV-1 PR 与五种不同抑制剂复合物的晶体结构，这些结构更紧凑，更有效。我们进行了详细的构效关系研究，以详细解释抑制剂和蛋白酶之间的极性和疏水相互作用的影响。
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