Institut für Pharmazeutische Chemie, Philipps-Universität Marburg , Marbacher Weg 6, 35032 Marburg, Germany.
J Med Chem. 2014 Jul 24;57(14):6266-72. doi: 10.1021/jm500402c. Epub 2014 Jul 9.
HTLV-1 protease (HTLV-1 PR) is an aspartic protease which represents a promising drug target for the discovery of novel anti-HTLV-1 drugs. The X-ray structure of HTLV-1 PR in complex with the well-known and approved HIV-1 PR inhibitor Indinavir was determined at 2.40 Å resolution. In this contribution, we describe the first crystal structure in complex with a nonpeptidic inhibitor that accounts for rationalizing the rather moderate affinity of Indinavir against HTLV-1 PR and provides the basis for further structure-guided optimization strategies.
人类嗜 T 细胞病毒 1 蛋白酶（HTLV-1 PR）是一种天冬氨酸蛋白酶，是发现新型抗 HTLV-1 药物的有希望的药物靶点。与众所周知且已批准的 HIV-1 PR 抑制剂茚地那韦结合的 HTLV-1 PR 的 X 射线结构在 2.40 Å 分辨率下确定。在本研究中，我们描述了第一个与非肽抑制剂结合的晶体结构，该结构解释了茚地那韦对 HTLV-1 PR 的亲和力相当中等的原因，并为进一步的结构导向优化策略提供了基础。
