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| ==ADP-dependent glucokinase from Pyrococcus horikoshii== | | ==ADP-dependent glucokinase from Pyrococcus horikoshii== |
- | <StructureSection load='5o0i' size='340' side='right' caption='[[5o0i]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='5o0i' size='340' side='right'caption='[[5o0i]], [[Resolution|resolution]] 2.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[5o0i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O0I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5o0i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii_OT3 Pyrococcus horikoshii OT3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O0I FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glkA, PH0589 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=70601 Pyrococcus horikoshii])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ADP-specific_glucokinase ADP-specific glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.147 2.7.1.147] </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=5o0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o0i OCA], [https://pdbe.org/5o0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o0i RCSB], [https://www.ebi.ac.uk/pdbsum/5o0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o0i 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=5o0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o0i OCA], [http://pdbe.org/5o0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o0i RCSB], [http://www.ebi.ac.uk/pdbsum/5o0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o0i ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/GLKA_PYRHO GLKA_PYRHO]] Catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor. | + | [https://www.uniprot.org/uniprot/GLKA_PYRHO GLKA_PYRHO] Catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor. |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: ADP-specific glucokinase]] | + | [[Category: Large Structures]] |
- | [[Category: Pyrococcus horikoshii]] | + | [[Category: Pyrococcus horikoshii OT3]] |
- | [[Category: Dubin, G]] | + | [[Category: Dubin G]] |
- | [[Category: Grudnik, P]] | + | [[Category: Grudnik P]] |
- | [[Category: Adp-dependent glucokinase]]
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- | [[Category: Transferase]]
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| Structural highlights
Function
GLKA_PYRHO Catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor.
Publication Abstract from PubMed
In higher eukaryotes, several ATP-utilizing enzymes known as hexokinases activate glucose in the glycolysis pathway by phosphorylation to glucose-6-phosphate. In contrast to canonical hexokinases which use ATP, ADP-dependent glucokinase (ADPGK) catalyzes non-canonical phosphorylation of glucose to glucose-6-phosphate using ADP as a phosphate donor. Initially discovered in Archaea, the human homolog of ADPGK was described only recently. ADPGK's involvement in modified bioenergetics of activated T cells has been postulated and elevated ADPGK expression has been reported in various cancer tissues. However, the physiological role of ADPGK is still poorly understood and effective ADPGK inhibitors still await discovery. Here we show that 8-bromo substituted adenosine nucleotide inhibits human ADPGK. By solving the crystal structure of archaeal ADPGK in complex with 8-bromoadenosine phosphate (8-Br-AMP) at 1.81 A resolution we identified the mechanism of inhibition. We observed that 8-Br-AMP is a competitive inhibitor of ADPGK and that the bromine substitution induces marked structural changes within the protein's active site by engaging crucial catalytic residues. The results obtained using Jurkat model of activated human T-cells suggest its moderate activity in cellular setting. We propose that our structural insights provide a critical basis for rational development of novel ADPGK inhibitors.
Structural basis for ADP-dependent glucokinase inhibition by 8-bromo-substituted adenosine nucleotide.,Grudnik P, Kaminski MM, Rembacz KP, Kuska K, Madej M, Potempa J, Dawidowski M, Dubin G J Biol Chem. 2018 May 21. pii: RA117.001562. doi: 10.1074/jbc.RA117.001562. PMID:29784881[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grudnik P, Kaminski MM, Rembacz KP, Kuska K, Madej M, Potempa J, Dawidowski M, Dubin G. Structural basis for ADP-dependent glucokinase inhibition by 8-bromo-substituted adenosine nucleotide. J Biol Chem. 2018 May 21. pii: RA117.001562. doi: 10.1074/jbc.RA117.001562. PMID:29784881 doi:http://dx.doi.org/10.1074/jbc.RA117.001562
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