|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4bc5' size='340' side='right'caption='[[4bc5]], [[Resolution|resolution]] 1.98Å' scene=''> | | <StructureSection load='4bc5' size='340' side='right'caption='[[4bc5]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bc5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BC5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bc5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BC5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5FX:5-DEOXY-5-FLUORO-D-XYLULOSE'>5FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.98Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4b6t|4b6t]], [[4b6y|4b6y]], [[4bc2|4bc2]], [[4bc3|4bc3]], [[4bc4|4bc4]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5FX:5-DEOXY-5-FLUORO-D-XYLULOSE'>5FX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Xylulokinase Xylulokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.17 2.7.1.17] </span></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=4bc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bc5 OCA], [https://pdbe.org/4bc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bc5 RCSB], [https://www.ebi.ac.uk/pdbsum/4bc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bc5 ProSAT]</span></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=4bc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bc5 OCA], [https://pdbe.org/4bc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bc5 RCSB], [https://www.ebi.ac.uk/pdbsum/4bc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bc5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/XYLB_HUMAN XYLB_HUMAN]] Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.<ref>PMID:23179721</ref>
| + | [https://www.uniprot.org/uniprot/XYLB_HUMAN XYLB_HUMAN] Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.<ref>PMID:23179721</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | D-Xylulokinase (XK; EC 2.7.1.17) catalyzes the ATP-dependent phosphorylation of D-xylulose (Xu) to produce xylulose-5-phosphate (Xu5P). In mammals, XK is the last enzyme in the glucuronate-xylulose pathway, active in the liver and kidneys, and is linked through its product Xu5P to the pentose phosphate pathway. XK may play an important role in metabolic disease, given that Xu5P is a key regulator of glucose metabolism and lipogenesis. We have expressed the product of a putative human XK gene, and identified it as the authentic human D-xylulokinase (hXK). NMR studies with a variety of sugars showed that hXK acts only on D-xylulose, and a coupled photometric assay established its key kinetic parameters as KM(Xu) = 24 +/- 3 muM and kcat = 35 +/- 5 s-1. Crystal structures were determined for hXK, on its own and in complexes with Xu, ADP and a fluorinated inhibitor. These reveal that hXK has two-domain fold characteristic of the sugar kinase/hsp70/actin superfamily, with glycerol kinase as its closest relative. Xu binds to domain-I and ADP to domain-II, but in this open form of hXK they are 10 A apart, implying that a large-scale conformational change is required for catalysis. Xu binds in its linear keto form, sandwiched between a Trp side chain and polar side chains that provide exquisite hydrogen bonding recognition. The hXK structure provides a basis for the design of specific inhibitors with which to probe its roles in sugar metabolism and metabolic disease.
| + | |
| - | | + | |
| - | Structure and function of human xylulokinase, an enzyme with important roles in carbohydrate metabolism.,Bunker RD, Bulloch EM, Dickson JM, Loomes KM, Baker EN J Biol Chem. 2012 Nov 23. PMID:23179721<ref>PMID:23179721</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4bc5" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Xylulokinase]]
| + | [[Category: Baker EN]] |
| - | [[Category: Baker, E N]] | + | [[Category: Bunker RD]] |
| - | [[Category: Bunker, R D]] | + | [[Category: Loomes KM]] |
| - | [[Category: Loomes, K M]] | + | |
| - | [[Category: Fggy carbohydrate kinase]]
| + | |
| - | [[Category: Glucuronate xylulokinase pathway]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Transferase]]
| + | |
