6r2u

Zinc-alpha2-Glycoprotein with a Fluorescent Dansyl C 11 Fatty Acid

spinqualitylabelsall models 6r2u, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6r2u is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Ligands: 11D, AZI, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ZA2G_HUMAN Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids. Publication Abstract from PubMed Human zinc-alpha2-glycoprotein (ZAG) is a 42 kDa adipokine which regulates body fat mass and is associated with cachexia and obesity. ZAG belongs to the major histocompatibility complex class I protein family and binds long-chain polyunsaturated fatty acids in its groove formed from the alpha1 and alpha2 domains. To identify the molecular basis of its lipid-binding function, we determined the first crystal structure at 2.49 A resolution for fatty acid-bound ZAG, where the ligand was the fluorescent 11-(dansylamino)undecanoic acid (DAUDA). The 192 kDa crystallographic asymmetric unit contained six ZAG and eight fatty acid molecules in unique conformations. Six fatty acid molecules were localised to the ZAG grooves, where their tails were bound in two distinct conformations. The carboxylate groups of three fatty acids projected out of the groove, while the fourth was hydrogen bonded with R73 inside the groove. Other ligand-residue contacts were primarily hydrophobic. A new fatty acid site was revealed for two further DAUDA molecules at the ZAG alpha3 domains. Following conformational changes from unbound ZAG, the alpha3 domains formed tetrameric beta-barrel structures lined by fatty acid molecules that doubled the binding capacity of ZAG. Analytical ultracentrifugation revealed that ZAG in solution was a monomer in the absence of DAUDA, but formed small amounts of tetramers with DAUDA. By showing that ZAG binds fatty acids in different locations, we demonstrate an augmented mechanism for fatty acid binding in ZAG that is distinct from other known fatty acid binding proteins, and may be relevant to cachexia. Crystal structure of zinc-alpha2-glycoprotein in complex with a fatty acid reveals multiple different modes of protein-lipid binding.,Lau AM, Zahid H, Gor J, Perkins SJ, Coker AR, McDermott LC Biochem J. 2019 Oct 15;476(19):2815-2834. doi: 10.1042/BCJ20190354. PMID:31506272 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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