Download MendeleyStructure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex.
Tan, Q., Zhu, Y., Li, J., Chen, Z., Han, G.W., Kufareva, I., Li, T., Ma, L., Fenalti, G., Li, J., Zhang, W., Xie, X., Yang, H., Jiang, H., Cherezov, V., Liu, H., Stevens, R.C., Zhao, Q., Wu, B.(2013) Science 341: 1387-1390
- PubMed: 24030490
- DOI: https://doi.org/10.1126/science.1241475
- Primary Citation of Related Structures:
4MBS - PubMed Abstract:
The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.
Organizational Affiliation:
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai, China 201203.
