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| | <StructureSection load='6wv5' size='340' side='right'caption='[[6wv5]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='6wv5' size='340' side='right'caption='[[6wv5]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wv5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aeqvi Aeqvi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WV5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WV5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wv5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WV5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UAV:(2R,3R)-2-hydroxy-3-methyl-2-[(2E,7S)-3,7,11,15-tetramethylhexadec-2-en-1-yl]-2,3-dihydronaphthalene-1,4-dione'>UAV</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]] 2.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CRO:{2-[(1R,2R)-1-AMINO-2-HYDROXYPROPYL]-4-(4-HYDROXYBENZYLIDENE)-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>CRO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CRO:{2-[(1R,2R)-1-AMINO-2-HYDROXYPROPYL]-4-(4-HYDROXYBENZYLIDENE)-5-OXO-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}ACETIC+ACID'>CRO</scene>, <scene name='pdbligand=UAV:(2R,3R)-2-hydroxy-3-methyl-2-[(2E,7S)-3,7,11,15-tetramethylhexadec-2-en-1-yl]-2,3-dihydronaphthalene-1,4-dione'>UAV</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gfp ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6100 AEQVI])</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=6wv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wv5 OCA], [https://pdbe.org/6wv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wv5 RCSB], [https://www.ebi.ac.uk/pdbsum/6wv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wv5 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Oxidoreductase Oxidoreductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.4 1.17.4.4] </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=6wv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wv5 OCA], [http://pdbe.org/6wv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wv5 RCSB], [http://www.ebi.ac.uk/pdbsum/6wv5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wv5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/VKOR1_HUMAN VKOR1_HUMAN] Prediction of resistance to vitamin K antagonists;Prediction of toxicity or dose selection of vitamin K antagonists;Hereditary combined deficiency of vitamin K-dependent clotting factors. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GFP_AEQVI GFP_AEQVI] Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.[https://www.uniprot.org/uniprot/VKOR1_HUMAN VKOR1_HUMAN] Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.<ref>PMID:14765194</ref> <ref>PMID:14765195</ref> <ref>PMID:15879509</ref> <ref>PMID:16270630</ref> <ref>PMID:20978134</ref> <ref>PMID:22923610</ref> <ref>PMID:33154105</ref> [https://www.uniprot.org/uniprot/K0NYR4_9CAUD K0NYR4_9CAUD] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6wv5" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6wv5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aeqvi]] | + | [[Category: Aequorea victoria]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Oxidoreductase]]
| + | [[Category: Li W]] |
| - | [[Category: Li, W]] | + | [[Category: Liu S]] |
| - | [[Category: Liu, S]] | + | [[Category: Sukumar N]] |
| - | [[Category: Sukumar, N]] | + | |
| - | [[Category: Fluorescent protein]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Superwarfarin]]
| + | |
| - | [[Category: Vitamin k]]
| + | |
| - | [[Category: Warfarin]]
| + | |
| Structural highlights
Disease
VKOR1_HUMAN Prediction of resistance to vitamin K antagonists;Prediction of toxicity or dose selection of vitamin K antagonists;Hereditary combined deficiency of vitamin K-dependent clotting factors. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
GFP_AEQVI Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin.VKOR1_HUMAN Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.[1] [2] [3] [4] [5] [6] [7] K0NYR4_9CAUD
Publication Abstract from PubMed
Vitamin K antagonists are widely used anticoagulants targeting vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, here we report eleven x-ray crystal structures of human VKOR and pufferfish VKOR-like with substrates and antagonists in different redox states. Substrates entering the active site in a partially oxidized state form a cysteine adduct that induces an open-to-closed conformational change, triggering reduction. Binding and catalysis is facilitated by hydrogen-bonding interactions in a hydrophobic pocket. The antagonists bind specifically to the same hydrogen-bonding residues and induce a similar closed conformation. Thus, vitamin K antagonists act through mimicking the key interactions and conformational changes required for the VKOR catalytic cycle.
Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation.,Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W Science. 2020 Nov 5. pii: science.abc5667. doi: 10.1126/science.abc5667. PMID:33154105[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Müller CR, Strom TM, Oldenburg J. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. PMID:14765194 doi:10.1038/nature02214
- ↑ Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW. Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. PMID:14765195 doi:10.1038/nature02254
- ↑ Pelz HJ, Rost S, Hünerberg M, Fregin A, Heiberg AC, Baert K, MacNicoll AD, Prescott CV, Walker AS, Oldenburg J, Müller CR. The genetic basis of resistance to anticoagulants in rodents. Genetics. 2005 Aug;170(4):1839-47. PMID:15879509 doi:10.1534/genetics.104.040360
- ↑ Rost S, Fregin A, Hünerberg M, Bevans CG, Müller CR, Oldenburg J. Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Thromb Haemost. 2005 Oct;94(4):780-6. PMID:16270630 doi:10.1160/TH05-02-0082
- ↑ Rishavy MA, Usubalieva A, Hallgren KW, Berkner KL. Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation. J Biol Chem. 2011 Mar 4;286(9):7267-78. PMID:20978134 doi:10.1074/jbc.M110.172213
- ↑ Tie JK, Jin DY, Stafford DW. Human vitamin K epoxide reductase and its bacterial homologue have different membrane topologies and reaction mechanisms. J Biol Chem. 2012 Oct 5;287(41):33945-55. PMID:22923610 doi:10.1074/jbc.M112.402941
- ↑ Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W. Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation. Science. 2020 Nov 5. pii: science.abc5667. doi: 10.1126/science.abc5667. PMID:33154105 doi:http://dx.doi.org/10.1126/science.abc5667
- ↑ Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W. Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation. Science. 2020 Nov 5. pii: science.abc5667. doi: 10.1126/science.abc5667. PMID:33154105 doi:http://dx.doi.org/10.1126/science.abc5667
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