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![[Figure 7]](gm5114fig7mag.jpg)
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Figure 7
Joint fatty-acid and fragment binding to FABP4_5. (a) The backbone for hFABP4_5 structure 7fxl is shown as a B-value putty for reference, with the lid (Met33) and latch (Leu58) indicated. Ligands with an acidic head group, the carboxylate in fatty acids, bind between residues Arg107, Arg127 and Tyr129, often with charged hydrogen bonds. The aliphatic part of the fatty acids wraps around the tip of Phe17 to adopt U- or L-shaped conformations. For the four hFABP4_5 structures 7fxl, 7fyh, 7g0x and 7g1p, the endogenous fatty acid was built as myristate, but the presence of longer fatty acids as a mixture and multiple alternate conformations cannot be excluded [straight arrows in (b)]. 7fyh, 7g0x and 7g1p contain an additional fragment with the chemical structures shown. The hFABP4 structure 7fz8 also has a fragment bound at this site, but the density for the fatty acid was insufficiently clear to warrant its building. (b) All of the fragments engage in hydrogen bonding to the side chain of Thr61 and bind edge-on to the side chain of Phe17 (not shown). Fragment binding is incompatible with the U shape, but the tip of the aliphatic moiety shifts upwards and points into solvent. This shift is not accompanied by a change in the latch conformation or the Leu58 rotamer, but flips the side chain of Met33 in the lid (dotted arrows). The Fo − Fc omit electron density for the fatty acid in 7fxl is contoured as an orange mesh at the 3 r.m.s.d. level. |
![[Figure 7]](gm5114fig7.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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