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| | <StructureSection load='6oid' size='340' side='right'caption='[[6oid]], [[Resolution|resolution]] 2.37Å' scene=''> | | <StructureSection load='6oid' size='340' side='right'caption='[[6oid]], [[Resolution|resolution]] 2.37Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6oid]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OID OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OID FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6oid]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OID FirstGlance]. <br> |
| - | </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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 2.365Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">At3g61080, T27I15_170 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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/Protein-ribulosamine_3-kinase Protein-ribulosamine 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.172 2.7.1.172] </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=6oid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oid OCA], [https://pdbe.org/6oid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oid RCSB], [https://www.ebi.ac.uk/pdbsum/6oid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oid ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6oid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oid OCA], [http://pdbe.org/6oid PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oid RCSB], [http://www.ebi.ac.uk/pdbsum/6oid PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oid ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FN3KR_ARATH FN3KR_ARATH]] Initiates a process leading to the deglycation of proteins (PubMed:15705060). Phosphorylates low-molecular-mass and protein-bound erythrulosamines and ribulosamines, but not fructosamines or psicosamines, on the third carbon of the sugar moiety (PubMed:15705060). Protein-bound erythrulosamine 3-phosphates and ribulosamine 3-phosphates are unstable and decompose under physiological conditions (PubMed:15705060).<ref>PMID:15705060</ref> | + | [https://www.uniprot.org/uniprot/FN3KR_ARATH FN3KR_ARATH] Initiates a process leading to the deglycation of proteins (PubMed:15705060). Phosphorylates low-molecular-mass and protein-bound erythrulosamines and ribulosamines, but not fructosamines or psicosamines, on the third carbon of the sugar moiety (PubMed:15705060). Protein-bound erythrulosamine 3-phosphates and ribulosamine 3-phosphates are unstable and decompose under physiological conditions (PubMed:15705060).<ref>PMID:15705060</ref> |
| | <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: Arath]] | + | [[Category: Arabidopsis thaliana]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-ribulosamine 3-kinase]]
| + | [[Category: Kadirvelraj R]] |
| - | [[Category: Kadirvelraj, R]] | + | [[Category: Shrestha S]] |
| - | [[Category: Shrestha, S]] | + | [[Category: Wood ZA]] |
| - | [[Category: Wood, Z A]] | + | |
| - | [[Category: Deglycation]]
| + | |
| - | [[Category: Fructosamine-3-kinase]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Phosphotransferase]]
| + | |
| - | [[Category: Plant protein]]
| + | |
| - | [[Category: Protein repair]]
| + | |
| - | [[Category: Small molecule kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
6oid is a 2 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.365Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
FN3KR_ARATH Initiates a process leading to the deglycation of proteins (PubMed:15705060). Phosphorylates low-molecular-mass and protein-bound erythrulosamines and ribulosamines, but not fructosamines or psicosamines, on the third carbon of the sugar moiety (PubMed:15705060). Protein-bound erythrulosamine 3-phosphates and ribulosamine 3-phosphates are unstable and decompose under physiological conditions (PubMed:15705060).[1]
Publication Abstract from PubMed
Aberrant regulation of metabolic kinases by altered redox homeostasis substantially contributes to aging and various diseases, such as diabetes. We found that the catalytic activity of a conserved family of fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases, is regulated by redox-sensitive cysteine residues in the kinase domain. The crystal structure of the FN3K homolog from Arabidopsis thaliana revealed that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining beta strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirmed that the strained disulfides function as redox "switches" to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, was also redox sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, were not. Furthermore, CRISPR-mediated knockout of FN3K in human liver cancer cells altered the abundance of redox metabolites, including an increase in glutathione. We propose that redox regulation evolved in FN3K homologs in response to changing cellular redox conditions. Our findings provide insights into the origin and evolution of redox regulation in the protein kinase superfamily and may open new avenues for targeting human FN3K in diabetic complications.
A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily.,Shrestha S, Katiyar S, Sanz-Rodriguez CE, Kemppinen NR, Kim HW, Kadirvelraj R, Panagos C, Keyhaninejad N, Colonna M, Chopra P, Byrne DP, Boons GJ, van der Knaap E, Eyers PA, Edison AS, Wood ZA, Kannan N Sci Signal. 2020 Jul 7;13(639). pii: 13/639/eaax6313. doi:, 10.1126/scisignal.aax6313. PMID:32636308[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fortpied J, Gemayel R, Stroobant V, van Schaftingen E. Plant ribulosamine/erythrulosamine 3-kinase, a putative protein-repair enzyme. Biochem J. 2005 Jun 15;388(Pt 3):795-802. doi: 10.1042/BJ20041976. PMID:15705060 doi:http://dx.doi.org/10.1042/BJ20041976
- ↑ Shrestha S, Katiyar S, Sanz-Rodriguez CE, Kemppinen NR, Kim HW, Kadirvelraj R, Panagos C, Keyhaninejad N, Colonna M, Chopra P, Byrne DP, Boons GJ, van der Knaap E, Eyers PA, Edison AS, Wood ZA, Kannan N. A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily. Sci Signal. 2020 Jul 7;13(639). pii: 13/639/eaax6313. doi:, 10.1126/scisignal.aax6313. PMID:32636308 doi:http://dx.doi.org/10.1126/scisignal.aax6313
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