4bme

Crystal structure of the N terminal domain of human Galectin 8, F19Y mutant

spinqualitylabelsall models 4bme, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bme is a 2 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 2Å Ligands: GAL, GLC, PRD_900008 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LEG8_HUMAN Lectin with a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans. Publication Abstract from PubMed Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence for association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically to rheumatoid arthritis, we here initiate the study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. We apply a strategically combined set of structural and cell biological techniques for comparing properties of the wild-type and variant proteins. The overall hydrodynamic behavior of the full-length protein and of the separate N-domain is not noticeably altered, but displacements in the F0 beta-strand of the beta-sandwich fold in the N-domain are induced, as evidenced by protein crystallography. Analysis of thermal stability by circular dichroism spectroscopy revealed perceptible differences for the full-length proteins, pointing to an impact of the substitution beyond the N-domain. In addition, small differences in thermodynamic parameters of carbohydrate binding are detected. On the level of two types of tumor cells, characteristics of binding appeared rather similar. In further comparison of the influence on proliferation, the variant proved to be more active as growth regulator in the six tested lines of neuroblastoma, erythroleukemia and colon adenocarcinoma. The seemingly subtle structural change identified here thus has functional implications in vitro, encouraging further analysis in autoimmune regulation and, in a broad context, in work with other natural single-site variants, using the documented combined strategy. DATABASE: The atomic coordinates and structure factors (codes 4BMB, 4BME) have been deposited in the Protein Data Bank. Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.,Ruiz FM, Scholz BA, Buzamet E, Kopitz J, Andre S, Menendez M, Romero A, Solis D, Gabius HJ FEBS J. 2014 Mar;281(5):1446-64. doi: 10.1111/febs.12716. Epub 2014 Feb 3. PMID:24418318 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Galectin 3D structures

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