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| <StructureSection load='4rqx' size='340' side='right'caption='[[4rqx]], [[Resolution|resolution]] 2.26Å' scene=''> | | <StructureSection load='4rqx' size='340' side='right'caption='[[4rqx]], [[Resolution|resolution]] 2.26Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4rqx]] is a 5 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=4RQX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RQX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rqx]] is a 5 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=4RQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RQX FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COM:1-THIOETHANESULFONIC+ACID'>COM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COM:1-THIOETHANESULFONIC+ACID'>COM</scene></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRDX4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4rqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rqx OCA], [https://pdbe.org/4rqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rqx RCSB], [https://www.ebi.ac.uk/pdbsum/4rqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rqx 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/Peroxiredoxin Peroxiredoxin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.15 1.11.1.15] </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=4rqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rqx OCA], [http://pdbe.org/4rqx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rqx RCSB], [http://www.ebi.ac.uk/pdbsum/4rqx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rqx ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/PRDX4_HUMAN PRDX4_HUMAN]] Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.<ref>PMID:9388242</ref> | + | [https://www.uniprot.org/uniprot/PRDX4_HUMAN PRDX4_HUMAN] Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.<ref>PMID:9388242</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | |
| ==See Also== | | ==See Also== |
- | *[[Peroxiredoxin|Peroxiredoxin]] | + | *[[Peroxiredoxin 3D structures|Peroxiredoxin 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Peroxiredoxin]]
| + | [[Category: Badger J]] |
- | [[Category: Badger, J]] | + | [[Category: Hausheer FH]] |
- | [[Category: Hausheer, F H]] | + | [[Category: Logan C]] |
- | [[Category: Logan, C]] | + | [[Category: Nienaber VL]] |
- | [[Category: Nienaber, V L]] | + | [[Category: Sridhar V]] |
- | [[Category: Sridhar, V]] | + | |
- | [[Category: Oxidoreductase]]
| + | |
- | [[Category: Thioredoxin]]
| + | |
| Structural highlights
Function
PRDX4_HUMAN Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.[1]
Publication Abstract from PubMed
Glutaredoxin (Grx), peroxiredoxin (Prx), and thioredoxin (Trx) are redoxin family proteins that catalyze different types of chemical reactions that impact cell growth and survival through functionally distinct intracellular pathways. Much research is focused on understanding the roles of these redoxin proteins in the development and/or progression of human diseases. Grx and Prx are overexpressed in human cancers, including human lung cancers. BNP7787 is a novel investigational agent that has been evaluated in previous clinical studies, including non-small cell lung cancer (NSCLC) studies. Herein, data from activity assays, mass spectrometry analyses, and X-ray crystallographic studies indicate that BNP7787 forms mixed disulfides with select cysteine residues on Grx and Prx and modulates their function. Studies of interactions between BNP7787 and Trx have been conducted and reported separately. Despite the fact that Trx, Grx, and Prx are functionally distinct proteins that impact oxidative stress, cell proliferation and disease processes through different intracellular pathways, BNP7787 can modify each protein and appears to modulate function through mechanisms that are unique to each target protein. Tumor cells are often genomically heterogeneous containing subpopulations of cancer cells that often express different tumor-promoting proteins or that have multiple dysregulated signaling pathways modulating cell proliferation and drug resistance. A multi-targeted agent that simultaneously modulates activity of proteins important in mediating cell proliferation by functionally distinct intracellular pathways could have many potentially useful therapeutic applications.
Cysteine Specific Targeting of the Functionally Distinct Peroxiredoxin and Glutaredoxin Proteins by the Investigational Disulfide BNP7787.,Parker AR, Petluru PN, Nienaber VL, Badger J, Leverett BD, Jair K, Sridhar V, Logan C, Ayala PY, Kochat H, Hausheer FH Molecules. 2015 Mar 18;20(3):4928-50. doi: 10.3390/molecules20034928. PMID:25793542[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jin DY, Chae HZ, Rhee SG, Jeang KT. Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem. 1997 Dec 5;272(49):30952-61. PMID:9388242
- ↑ Parker AR, Petluru PN, Nienaber VL, Badger J, Leverett BD, Jair K, Sridhar V, Logan C, Ayala PY, Kochat H, Hausheer FH. Cysteine Specific Targeting of the Functionally Distinct Peroxiredoxin and Glutaredoxin Proteins by the Investigational Disulfide BNP7787. Molecules. 2015 Mar 18;20(3):4928-50. doi: 10.3390/molecules20034928. PMID:25793542 doi:http://dx.doi.org/10.3390/molecules20034928
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