| Structural highlights
Function
[OFUT2_CAEEL] 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 I repeats (TSRs) where C1 and C2 are the first and second cysteines of the repeat, respectively. O-fucosylates members of several protein families including the ADAMTS superfamily and the thrombosporin (TSP) and spondin families. Required for the proper secretion of ADAMTS family members such as ADAMSL1 and ADAMST13 (By similarity).[1]
Publication Abstract from PubMed
Protein O-fucosyltransferase 2 (POFUT2) is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats (TSRs). To date, the mechanism by which this enzyme recognizes very dissimilar TSRs has been unclear. By engineering a fusion protein, we report the crystal structure of Caenorhabditis elegans POFUT2 (CePOFUT2) in complex with GDP and human TSR1 that suggests an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the TSR1 is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex. Site-directed mutagenesis demonstrates that POFUT2 fucosylates threonine preferentially over serine and relies on folded TSRs containing the minimal consensus sequence C-X-X-S/T-C. Crystallographic and mutagenesis data, together with atomic-level simulations, uncover a binding mechanism by which POFUT2 promiscuously recognizes the structural fingerprint of poorly homologous TSRs through a dynamic network of water-mediated interactions.
A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2.,Valero-Gonzalez J, Leonhard-Melief C, Lira-Navarrete E, Jimenez-Oses G, Hernandez-Ruiz C, Pallares MC, Yruela I, Vasudevan D, Lostao A, Corzana F, Takeuchi H, Haltiwanger RS, Hurtado-Guerrero R Nat Chem Biol. 2016 Feb 8. doi: 10.1038/nchembio.2019. PMID:26854667[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Menzel O, Vellai T, Takacs-Vellai K, Reymond A, Mueller F, Antonarakis SE, Guipponi M. The Caenorhabditis elegans ortholog of C21orf80, a potential new protein O-fucosyltransferase, is required for normal development. Genomics. 2004 Aug;84(2):320-30. PMID:15233996 doi:http://dx.doi.org/10.1016/j.ygeno.2004.04.002
- ↑ Valero-Gonzalez J, Leonhard-Melief C, Lira-Navarrete E, Jimenez-Oses G, Hernandez-Ruiz C, Pallares MC, Yruela I, Vasudevan D, Lostao A, Corzana F, Takeuchi H, Haltiwanger RS, Hurtado-Guerrero R. A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2. Nat Chem Biol. 2016 Feb 8. doi: 10.1038/nchembio.2019. PMID:26854667 doi:http://dx.doi.org/10.1038/nchembio.2019
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