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| | ==X-ray crystal structure of Halotag bound to the P1 benzoxadiazole fluorogenic ligand== | | ==X-ray crystal structure of Halotag bound to the P1 benzoxadiazole fluorogenic ligand== |
| - | <StructureSection load='5vnp' size='340' side='right' caption='[[5vnp]], [[Resolution|resolution]] 2.23Å' scene=''> | + | <StructureSection load='5vnp' size='340' side='right'caption='[[5vnp]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vnp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_mycoides_roseum"_grotenfelt_1889 "bacterium mycoides roseum" grotenfelt 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VNP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vnp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodococcus_rhodochrous Rhodococcus rhodochrous]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VNP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VNP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9FM:N-{2-[2-(hexyloxy)ethoxy]ethyl}-N~2~-methyl-N~2~-{[7-(methylamino)-2,1,3-benzoxadiazol-4-yl]sulfonyl}glycinamide'>9FM</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.23Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dhaA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1829 "Bacterium mycoides roseum" Grotenfelt 1889])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9FM:~{N}-[2-(2-hexoxyethoxy)ethyl]-2-[methyl-[[7-(methylamino)-2,1,3-benzoxadiazol-4-yl]sulfonyl]amino]ethanamide'>9FM</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Haloalkane_dehalogenase Haloalkane dehalogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.8.1.5 3.8.1.5] </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=5vnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vnp OCA], [https://pdbe.org/5vnp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vnp RCSB], [https://www.ebi.ac.uk/pdbsum/5vnp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vnp 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=5vnp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vnp OCA], [http://pdbe.org/5vnp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vnp RCSB], [http://www.ebi.ac.uk/pdbsum/5vnp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vnp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DHAA_RHORH DHAA_RHORH]] Catalyzes hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons. Expresses halogenase activity against 1-chloroalkanes of chain length C3 to C10, and also shows a very weak activity with 1,2-dichloroethane. | + | [https://www.uniprot.org/uniprot/DHAA_RHORH DHAA_RHORH] Catalyzes hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons. Expresses halogenase activity against 1-chloroalkanes of chain length C3 to C10, and also shows a very weak activity with 1,2-dichloroethane. |
| | <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 5vnp" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5vnp" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dehalogenase 3D structures|Dehalogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacterium mycoides roseum grotenfelt 1889]] | + | [[Category: Large Structures]] |
| - | [[Category: Haloalkane dehalogenase]] | + | [[Category: Rhodococcus rhodochrous]] |
| - | [[Category: Boal, A K]] | + | [[Category: Boal AK]] |
| - | [[Category: Dunham, N P]] | + | [[Category: Dunham NP]] |
| - | [[Category: Biosensor]]
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| - | [[Category: Cytotoxicity]]
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| - | [[Category: Fluorescent probe]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Protein aggregation]]
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| - | [[Category: Proteome stress]]
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| Structural highlights
Function
DHAA_RHORH Catalyzes hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons. Expresses halogenase activity against 1-chloroalkanes of chain length C3 to C10, and also shows a very weak activity with 1,2-dichloroethane.
Publication Abstract from PubMed
Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins.
AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress.,Liu Y, Fares M, Dunham NP, Gao Z, Miao K, Jiang X, Bollinger SS, Boal AK, Zhang X Angew Chem Int Ed Engl. 2017 Jul 17;56(30):8672-8676. doi:, 10.1002/anie.201702417. Epub 2017 Jun 19. PMID:28557281[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu Y, Fares M, Dunham NP, Gao Z, Miao K, Jiang X, Bollinger SS, Boal AK, Zhang X. AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress. Angew Chem Int Ed Engl. 2017 Jul 17;56(30):8672-8676. doi:, 10.1002/anie.201702417. Epub 2017 Jun 19. PMID:28557281 doi:http://dx.doi.org/10.1002/anie.201702417
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