5foe

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the C. elegans Protein O-fucosyltransferase 2 (CePOFUT2) double mutant (R298K-R299K) in complex with GDP and the human TSR1 from thrombospondin 1

Structural highlights

5foe is a 2 chain structure with sequence from Caenorhabditis elegans and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.98Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TSP1_HUMAN Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.^[1] ^[2] 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).^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Simantov R, Febbraio M, Crombie R, Asch AS, Nachman RL, Silverstein RL. Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. J Clin Invest. 2001 Jan;107(1):45-52. PMID:11134179 doi:http://dx.doi.org/10.1172/JCI9061
↑ Kvansakul M, Adams JC, Hohenester E. Structure of a thrombospondin C-terminal fragment reveals a novel calcium core in the type 3 repeats. EMBO J. 2004 Mar 24;23(6):1223-33. Epub 2004 Mar 11. PMID:15014436 doi:http://dx.doi.org/10.1038/sj.emboj.7600166
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5foe"

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 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/OFUT2_CAEEL 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).<ref>PMID:15233996</ref> [https://www.uniprot.org/uniprot/TSP1_HUMAN TSP1_HUMAN] Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.<ref>PMID:11134179</ref> <ref>PMID:15014436</ref>
+[https://www.uniprot.org/uniprot/TSP1_HUMAN TSP1_HUMAN] Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.<ref>PMID:11134179</ref> <ref>PMID:15014436</ref> [https://www.uniprot.org/uniprot/OFUT2_CAEEL 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).<ref>PMID:15233996</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

5foe

From Proteopedia

Current revision

Crystal structure of the C. elegans Protein O-fucosyltransferase 2 (CePOFUT2) double mutant (R298K-R299K) in complex with GDP and the human TSR1 from thrombospondin 1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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