CCR5 structure

Yi Y, Singh A, Shaheen F, Louden A, Lee C, Collman RG. Contrasting use of CCR5 structural determinants by R5 and R5X4 variants within a human immunodeficiency virus type 1 primary isolate quasispecies. J Virol 2003 77(22) 12057-12066. 

FIGURE 7.3 Diversity of structures that interact with the (a) HIV reverse transcriptase inhibitor binding site [8] and (b) the CCR5 receptor mediating HIV-1 fusion [9],... 

Finke, P. E., Oates, B., Mills, S. G., MacCoss, M., Malkowitz, L., Springer, M. S., Gould, S. L., DeMartino, J. A., Carella, A. Carver, G., et al. (2001). Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4 synthesis and structure—Activity relationships for l-[7V-(Methyl)-7V-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(7V-(alkyl)-7V-(benzylox-ycarbonyl)amino)piperidin-l-yl)butanes. Bioorg. Med. Chem. Lett. 11 2475-2479. 

Roux KH, Taylor KA (2007) AIDS virus envelope spike structure. Curr Opin Struct Biol 17 244-252 Sacktor N, Haughey N, Cutler R, Tamara A, Turchan J, Pardo C, Vargas D, Nath A (2004) Novel markers of oxidative stress in actively progressive HIV dementia. J Neuroimmunol 157 176-184 Samson M, LaRosa G, Libert F, Paindavoine P, Detheux M, Vassart G, Parmentier M (1997) The second extraceUular loop of CCR5 is the major determinant of ligand specificity. J Biol Chem 272 24934-24941... 

We have been interested in studying the structure of the D6 chemokine receptor (7). This receptor has not, so far, been implicated in pathologies as prominent as those involving CCR5 and CXCR4. Nevertheless, it is structurally very similar to the other chemokine receptors and thus a three-dimensional structure of D6 would be an invaluable template that would facilitate the determination of the structure of other chemokine receptors. A major advantage of D6 over the other chemokine receptors is that it can be expressed to extremely... 

Govaerts C, Blanpain C, Deupi X, et al. The TXP motif in the second transmembrane helix of CCR5. A structural determinant of chemokine-induced activation. J Biol Chem 2001 276(16) 13217-13225. 

Oppermann M. Chemokine receptor CCR5 insights into structure, function, and regulation. Cell Signal 2004 16(11) 1201-1210. 

Lee B, Sharron M, Blanpain C, et al. Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function. J Biol Chem 1999 274(14) 9617-9626. 

Fig. 4. Structure of UK-427,857 (maraviroc), a CCR5-specific antagonist from Pfizer currently in phase III studies for HIV treatment. The original hit from the high-throughput screening, compound UK107,543, is also shown.

Many other families of CCR5 antagonists have been described in the last several years. Selected structures are provided along with references. 

Nonpeptide CCR5 Receptor Agonists by Structure-Based Virtual Screening. J. Med. Chem. 2007, 50, 1294-1303. 

It has been reported that the N-terminal CCR5, the coreceptor for binding of CD4-gpl20 complex, is tyrosine rich and the tyrosines are posttranslationally converted to sulfated tyrosines (54-56). The NMR, X-ray, and docking-based structure of the... 

Fig. 12 Structures of two phenylsulfonate-based inhibitors targeted to CCR5...

Kellenberger E, Springael JY, Parmentier M et al (2007) Identification of nonpeptide CCR5 receptor agonists by structure-based virtual screening. J Med Chem 50 1294-1303... 

Huang CC, Lam SN, Acharya P et al (2007) Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gpl20 and CD4. Science 317 1930-1934... 

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