TY - JOUR AU - Zhu Ya AU - Zhao Yan-long AU - Li Jian AU - Liu Hong AU - Zhao Qiang AU - Wu Bei-li AU - Yang Zhen-lin PY - 2019 TI - Molecular binding mode of PF-232798, a clinical anti-HIV candidate, at chemokine receptor CCR5 JF - Acta Pharmacologica Sinica; Vol 40, No 4 (April 2019): Acta Pharmacologica Sinica Y2 - 2019 KW - N2 - The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency virus) drug target owning to its pivotal role in HIV-1 viral entry as a co-receptor. Here, we present a 2.9 Å resolution crystal structure of CCR5 bound to PF-232798, a second-generation oral CCR5 antagonist currently in phase II clinical trials. PF-232798 and the marketed HIV drug maraviroc share a similar tropane scaffold with different amino (N)- and carboxyl (C)- substituents. Comparison of the CCR5–PF-232798 structure with the previously determined structure of CCR5 in complex with maraviroc reveals different binding modes of the two allosteric antagonists and subsequent conformational changes of the receptor. Our results not only offer insights into the phenomenon that PF-232798 has higher affinity and alternative resistance profile to maraviroc, but also will facilitate the design of new anti-HIV drugs. UR - http://www.chinaphar.com/article/view/9955