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| | <StructureSection load='6max' size='340' side='right'caption='[[6max]], [[Resolution|resolution]] 1.42Å' scene=''> | | <StructureSection load='6max' size='340' side='right'caption='[[6max]], [[Resolution|resolution]] 1.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6max]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Thema Thema]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MAX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6max]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima_MSB8 Thermotoga maritima MSB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MAX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9TF:Purpurin'>9TF</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]] 1.42Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nz0|1nz0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9TF:Purpurin'>9TF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rnpA, TM_1463 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</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=6max FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6max OCA], [https://pdbe.org/6max PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6max RCSB], [https://www.ebi.ac.uk/pdbsum/6max PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6max 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/Ribonuclease_P Ribonuclease P], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.26.5 3.1.26.5] </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=6max FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6max OCA], [http://pdbe.org/6max PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6max RCSB], [http://www.ebi.ac.uk/pdbsum/6max PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6max ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RNPA_THEMA RNPA_THEMA]] RNaseP catalyzes the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5'-terminus. It can also cleave other RNA substrates such as 4.5S RNA. The protein component plays an auxiliary but essential role in vivo by binding to the 5'-leader sequence and broadening the substrate specificity of the ribozyme (By similarity). | + | [https://www.uniprot.org/uniprot/RNPA_THEMA RNPA_THEMA] RNaseP catalyzes the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5'-terminus. It can also cleave other RNA substrates such as 4.5S RNA. The protein component plays an auxiliary but essential role in vivo by binding to the 5'-leader sequence and broadening the substrate specificity of the ribozyme (By similarity). |
| | <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 6max" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6max" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ribonuclease 3D structures|Ribonuclease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ribonuclease P]] | + | [[Category: Thermotoga maritima MSB8]] |
| - | [[Category: Thema]]
| + | [[Category: Madrigal-Carrillo EA]] |
| - | [[Category: Madrigal-Carrillo, E A]] | + | [[Category: Torres-Larios A]] |
| - | [[Category: Torres-Larios, A]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: P protein]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| Structural highlights
Function
RNPA_THEMA RNaseP catalyzes the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5'-terminus. It can also cleave other RNA substrates such as 4.5S RNA. The protein component plays an auxiliary but essential role in vivo by binding to the 5'-leader sequence and broadening the substrate specificity of the ribozyme (By similarity).
Publication Abstract from PubMed
Ribonucleoprotein (RNP) complexes and RNA-processing enzymes are attractive targets for antibiotic development owing to their central roles in microbial physiology. For many of these complexes, comprehensive strategies to identify inhibitors are either lacking or suffer from substantial technical limitations. Here, we describe an activity-binding-structure platform for bacterial ribonuclease P (RNase P), an essential RNP ribozyme involved in 5' tRNA processing. A novel, real-time fluorescence-based assay was used to monitor RNase P activity and rapidly identify inhibitors using a mini-helix and a pre-tRNA-like bipartite substrate. Using the mini-helix substrate, we screened a library comprising 2560 compounds. Initial hits were then validated using pre-tRNA and the pre-tRNA-like substrate, which ultimately verified four compounds as inhibitors. Biolayer interferometry-based binding assays and molecular dynamics simulations were then used to characterize the interactions between each validated inhibitor and the P protein, P RNA and pre-tRNA. X-ray crystallographic studies subsequently elucidated the structure of the P protein bound to the most promising hit, purpurin, and revealed how this inhibitor adversely affects tRNA 5' leader binding. This integrated platform affords improved structure-function studies of RNA processing enzymes and facilitates the discovery of novel regulators or inhibitors.
A screening platform to monitor RNA processing and protein-RNA interactions in ribonuclease P uncovers a small molecule inhibitor.,Madrigal-Carrillo EA, Diaz-Tufinio CA, Santamaria-Suarez HA, Arciniega M, Torres-Larios A Nucleic Acids Res. 2019 Apr 18. pii: 5475076. doi: 10.1093/nar/gkz285. PMID:30997498[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Madrigal-Carrillo EA, Diaz-Tufinio CA, Santamaria-Suarez HA, Arciniega M, Torres-Larios A. A screening platform to monitor RNA processing and protein-RNA interactions in ribonuclease P uncovers a small molecule inhibitor. Nucleic Acids Res. 2019 Apr 18. pii: 5475076. doi: 10.1093/nar/gkz285. PMID:30997498 doi:http://dx.doi.org/10.1093/nar/gkz285
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