4ap6

Crystal structure of human POFUT2 E54A mutant in complex with GDP- fucose

spinqualitylabelsall models 4ap6, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ap6 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, GFB, NAG Related: 4ap5 Activity: Peptide-O-fucosyltransferase, with EC number 2.4.1.221 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [OFUT2_HUMAN] Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue in the consensus sequence C1-X(2,3)-S/T-C2-X(2)-G of thrombospondin type 1 repeats where C1 and C2 are the first and second cysteines, respectively. O-fucosylates members of several protein families including the ADAMTS family, the thrombosporin (TSP) and spondin families. The O-fucosylation of TSRs is also required for restricting epithelial to mesenchymal transition (EMT), maintaining the correct patterning of mesoderm and localization of the definite endoderm (By similarity). Required for the proper secretion of ADAMTS family members such as ADAMSL1 and ADAMST13. Publication Abstract from PubMed Protein O-fucosylation is a post-translational modification found on serine/threonine residues of thrombospondin type 1 repeats (TSR). The fucose transfer is catalysed by the enzyme protein O-fucosyltransferase 2 (POFUT2) and >40 human proteins contain the TSR consensus sequence for POFUT2-dependent fucosylation. To better understand O-fucosylation on TSR, we carried out a structural and functional analysis of human POFUT2 and its TSR substrate. Crystal structures of POFUT2 reveal a variation of the classical GT-B fold and identify sugar donor and TSR acceptor binding sites. Structural findings are correlated with steady-state kinetic measurements of wild-type and mutant POFUT2 and TSR and give insight into the catalytic mechanism and substrate specificity. By using an artificial mini-TSR substrate, we show that specificity is not primarily encoded in the TSR protein sequence but rather in the unusual 3D structure of a small part of the TSR. Our findings uncover that recognition of distinct conserved 3D fold motifs can be used as a mechanism to achieve substrate specificity by enzymes modifying completely folded proteins of very wide sequence diversity and biological function. Structure of human POFUT2: insights into thrombospondin type 1 repeat fold and O-fucosylation.,Chen CI, Keusch JJ, Klein D, Hess D, Hofsteenge J, Gut H EMBO J. 2012 May 15. doi: 10.1038/emboj.2012.143. PMID:22588082 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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