2ch5

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[[Image:2ch5.gif|left|200px]]<br /><applet load="2ch5" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2ch5, resolution 1.90&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN N-ACETYLGLUCOSAMINE KINASE IN COMPLEX WITH N-ACETYLGLUCOSAMINE'''<br />
 
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==Overview==
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==Crystal structure of human N-acetylglucosamine kinase in complex with N-acetylglucosamine==
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N-Acetylglucosamine (GlcNAc), a major component of complex carbohydrates, is synthesized de novo or salvaged from lysosomally degraded, glycoconjugates and from nutritional sources. The salvage pathway requires, that GlcNAc kinase converts GlcNAc to GlcNAc-6-phosphate, a component, utilized in UDP-GlcNAc biosynthesis or energy metabolism. GlcNAc kinase, belongs to the sugar kinase/Hsp70/actin superfamily that catalyze, phosphoryl transfer from ATP to their respective substrates, and in most, cases catalysis is associated with a large conformational change in which, the N-terminal small and C-terminal large domains enclose the substrates., Here we report two crystal structures of homodimeric human GlcNAc kinase, one in complex with GlcNAc and the other in complex with ADP and glucose., The active site of GlcNAc kinase is located in a deep cleft between the, two domains of the V-shaped monomer. The enzyme adopts a "closed", configuration in the GlcNAc-bound complex and GlcNAc interacts with, residues of both domains. In addition, the N-acetyl methyl group contacts, residues of the other monomer in the homodimer, a unique feature compared, to other members of the sugar kinase/Hsp70/actin superfamily. This, contrasts an "open" configuration in the ADP/glucose-bound structure, where glucose cannot form these interactions, explaining its low binding, affinity for GlcNAc kinase. Our results support functional implications, derived from apo crystal structures of GlcNAc kinases from Chromobacter, violaceum and Porphyromonas gingivalis and show that Tyr205, which is, phosphorylated in thrombin-activated platelets, lines the GlcNAc binding, pocket. This suggests that phosphorylation of Tyr205 may modulate GlcNAc, kinase activity and/or specificity.
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<StructureSection load='2ch5' size='340' side='right'caption='[[2ch5]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2ch5]] is a 4 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=2CH5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CH5 FirstGlance]. <br>
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2CH5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NDG:'>NDG</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-acetylglucosamine_kinase N-acetylglucosamine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.59 2.7.1.59] Known structural/functional Site: <scene name='pdbsite=AC1:Gol+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CH5 OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ch5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ch5 OCA], [https://pdbe.org/2ch5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ch5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ch5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ch5 ProSAT]</span></td></tr>
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Structures of human N-Acetylglucosamine kinase in two complexes with N-Acetylglucosamine and with ADP/glucose: insights into substrate specificity and regulation., Weihofen WA, Berger M, Chen H, Saenger W, Hinderlich S, J Mol Biol. 2006 Dec 1;364(3):388-99. Epub 2006 Sep 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17010375 17010375]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NAGK_HUMAN NAGK_HUMAN] Converts endogenous N-acetylglucosamine (GlcNAc), a major component of complex carbohydrates, from lysosomal degradation or nutritional sources into GlcNAc 6-phosphate. Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway: although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded. Also has ManNAc kinase activity.<ref>PMID:22692205</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2ch5_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ch5 ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: N-acetylglucosamine kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Berger M]]
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[[Category: Berger, M.]]
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[[Category: Chen H]]
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[[Category: Chen, H.]]
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[[Category: Hinderlich S]]
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[[Category: Hinderlich, S.]]
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[[Category: Saenger W]]
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[[Category: Saenger, W.]]
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[[Category: Weihofen WA]]
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[[Category: Weihofen, W.A.]]
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[[Category: GOL]]
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[[Category: NAG]]
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[[Category: NDG]]
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[[Category: closed conformation]]
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[[Category: domain rotation]]
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[[Category: glcnac]]
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[[Category: hypothetical protein]]
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[[Category: n-acetylglucosamine]]
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[[Category: open conformation]]
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[[Category: ribonuclease h fold]]
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[[Category: sugar kinase]]
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[[Category: sugar kinase/hsp70/actin superfamily]]
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[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:35:15 2008''
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Current revision

Crystal structure of human N-acetylglucosamine kinase in complex with N-acetylglucosamine

PDB ID 2ch5

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