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2ch6

From Proteopedia

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Current revision

Crystal structure of human N-acetylglucosamine kinase in complex with ADP and glucose

Structural highlights

2ch6 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.72Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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:17010375^[2]

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

References

↑ Bergfeld AK, Pearce OM, Diaz SL, Pham T, Varki A. Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating the intracellular fate of the non-human sialic acid N-glycolylneuraminic acid. J Biol Chem. 2012 Aug 17;287(34):28865-81. doi: 10.1074/jbc.M112.363549. Epub, 2012 Jun 12. PMID:22692205 doi:http://dx.doi.org/10.1074/jbc.M112.363549
↑ Weihofen WA, Berger M, Chen H, Saenger W, Hinderlich S. Structures of human N-Acetylglucosamine kinase in two complexes with N-Acetylglucosamine and with ADP/glucose: insights into substrate specificity and regulation. J Mol Biol. 2006 Dec 1;364(3):388-99. Epub 2006 Sep 3. PMID:17010375 doi:10.1016/j.jmb.2006.08.085

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ch6"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF HUMAN N-ACETYLGLUCOSAMINE KINASE IN COMPLEX WITH ADP AND GLUCOSE==
-<StructureSection load='2ch6' size='340' side='right' caption='[[2ch6]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
+==Crystal structure of human N-acetylglucosamine kinase in complex with ADP and glucose==
+<StructureSection load='2ch6' size='340' side='right'caption='[[2ch6]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ch6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CH6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CH6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ch6]] 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=2CH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CH6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</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]] 2.72&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ch5|2ch5]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=2ch6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ch6 OCA], [https://pdbe.org/2ch6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ch6 RCSB], [https://www.ebi.ac.uk/pdbsum/2ch6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ch6 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ch6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ch6 OCA], [http://pdbe.org/2ch6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ch6 RCSB], [http://www.ebi.ac.uk/pdbsum/2ch6 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2ch6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2ch6_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2ch6 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 33: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: N-acetylglucosamine kinase]]
+[[Category: Large Structures]]
-[[Category: Berger, M]]
+[[Category: Berger M]]
-[[Category: Chen, H]]
+[[Category: Chen H]]
-[[Category: Hinderlich, S]]
+[[Category: Hinderlich S]]
-[[Category: Saenger, W]]
+[[Category: Saenger W]]
-[[Category: Weihofen, W A]]
+[[Category: Weihofen WA]]
-[[Category: Ribonuclease h fold]]
-[[Category: Sugar kinase]]
-[[Category: Sugar kinase/hsp70/actin superfamily]]
-[[Category: Transferase]]

2ch6

From Proteopedia

Current revision

Crystal structure of human N-acetylglucosamine kinase in complex with ADP and glucose

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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