View source for 9iip


==Fucokinase part of FKP with beta-L-fucose 1-phosphate==
<StructureSection load='9iip' size='340' side='right'caption='[[9iip]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9iip]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9IIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9IIP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ED6:6-deoxy-1-O-phosphono-beta-L-galactopyranose'>ED6</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9iip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9iip OCA], [https://pdbe.org/9iip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9iip RCSB], [https://www.ebi.ac.uk/pdbsum/9iip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9iip ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FKP_BACFG FKP_BACFG] Bifunctional enzyme involved in the salvage pathway of GDP-fucose synthesis. Catalyzes two successive reactions, the ATP-dependent phosphorylation of L-fucose to L-fucose 1-phosphate, and its guanylylation to GDP-L-fucose. GDP-fucose is an important fucose donor in the process of fucosylated oligosaccharides formation.<ref>PMID:30242642</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The bifunctional L-fucokinase/GDP-beta-L-fucose pyrophosphorylase (FKP) from Bacteroides fragilis catalyzes the conversion from L-fucose to GDP-beta-L-fucose. The reaction product, representing the activated form of L-fucose, is used by all L-fucosyltransferases to incorporate L-fucose. Herein we report the first X-ray crystal structures of FKP in complex with substrate/product, leading to the dissection of both activity domains and corresponding catalytic mechanisms. The full length (FKP-FL, 949 amino acids) exists as a tetramer in solution, but the individually prepared N-terminal domain (FKP-NTD corresponding to the sequence 1-496, also containing a SUMO tag) and C-terminal (FKP-CTD, the sequence 519-949) form a monomer and a dimer, respectively. FKP-NTD has a single alpha/beta domain and a beta-helix-containing domain, whereas FKP-CTD folds into two alpha/beta domains and the linker comprises three alpha-helices. The beta-L-fucose-1-phosphate (fucose-1-P) and GTP bound separately to the active sites of fucokinase (located at FKP-CTD) and pyrophosphorylase (FKP-NTD), and a third nucleotide binding site is adjacent to the beta-helix (also in FKP-NTD). Furthermore, Asp762 was proposed to serve as the general base in the reaction of fucokinase, to deprotonate the C1-OH of fucose in the nucleophilic attack to gamma-phosphate of ATP, resulting in the formation of fucose-1-P. At the same time, Arg592 and magnesium ion stabilize the developing negative charge in the leaving group (ADP). Subsequently, in the pyrophosphorylase-catalyzed reaction, the Lys187 side chain facilitates the nucleophilic attack of fucose-1-P toward GTP, leading to the formation of GDP-fucose.

Structural Insight into the Catalytic Mechanism of the Bifunctional Enzyme L-Fucokinase/GDP-fucose Pyrophosphorylase.,Lin SW, Ko TP, Chiang HY, Wu CG, Hsu MF, Wang AH, Lin CH J Biol Chem. 2025 Feb 22:108344. doi: 10.1016/j.jbc.2025.108344. PMID:39993526<ref>PMID:39993526</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9iip" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacteroides fragilis]]
[[Category: Large Structures]]
[[Category: Hsu MF]]
[[Category: Ko TP]]
[[Category: Lin CH]]
[[Category: Lin SW]]