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| | ==Crystal Structure of AMPPNP-bound Human PRPF4B kinase domain== | | ==Crystal Structure of AMPPNP-bound Human PRPF4B kinase domain== |
| - | <StructureSection load='4iir' size='340' side='right' caption='[[4iir]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4iir' size='340' side='right'caption='[[4iir]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iir]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IIR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IIR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iir]] is a 2 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=4IIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IIR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ian|4ian]], [[4ifc|4ifc]], [[4ijp|4ijp]]</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=4iir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iir OCA], [https://pdbe.org/4iir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iir RCSB], [https://www.ebi.ac.uk/pdbsum/4iir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iir ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA0536, PRP4, PRP4H, PRP4K, PRPF4B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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| - | <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=4iir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iir OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iir RCSB], [http://www.ebi.ac.uk/pdbsum/4iir PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Function == | |
| - | [[http://www.uniprot.org/uniprot/PRP4B_HUMAN PRP4B_HUMAN]] Has a role in pre-mRNA splicing. Phosphorylates SF2/ASF. | |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4iir" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, X]] | + | [[Category: Chen X]] |
| - | [[Category: Haas, K]] | + | [[Category: Haas K]] |
| - | [[Category: McLean, L]] | + | [[Category: McLean L]] |
| - | [[Category: Mechin, I]] | + | [[Category: Mechin I]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Kinase]]
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| - | [[Category: Transferase]]
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| Structural highlights
Publication Abstract from PubMed
PRP4 kinase is known for its roles in regulating pre-mRNA splicing and beyond. Therefore, a wider spectrum of PRP4 kinase substrates could be expected. The role of PRP4 kinase in cancer is also yet to be fully elucidated. Attaining specific and potent PRP4 inhibitors would greatly facilitate the study of PRP4 biological function and its validation as a credible cancer target. In this report, we verified the requirement of enzymatic activity of PRP4 in regulating cancer cell growth and identified an array of potential novel substrates through orthogonal proteomics approaches. The ensuing effort in structural biology unveiled for the first time unique features of PRP4 kinase domain and its potential mode of interaction with a low molecular weight inhibitor. These results provide new and important information for further exploration of PRP4 kinase function in cancer.
Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches.,Gao Q, Mechin I, Kothari N, Guo Z, Deng G, Haas K, McManus J, Hoffmann D, Wang A, Wiederschain D, Rocnik J, Czechtizky W, Chen X, McLean L, Arlt H, Harper D, Liu F, Majid T, Patel V, Lengauer C, Garcia-Echeverria C, Zhang B, Cheng H, Dorsch M, Huang SM J Biol Chem. 2013 Sep 3. PMID:24003220[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gao Q, Mechin I, Kothari N, Guo Z, Deng G, Haas K, McManus J, Hoffmann D, Wang A, Wiederschain D, Rocnik J, Czechtizky W, Chen X, McLean L, Arlt H, Harper D, Liu F, Majid T, Patel V, Lengauer C, Garcia-Echeverria C, Zhang B, Cheng H, Dorsch M, Huang SM. Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches. J Biol Chem. 2013 Sep 3. PMID:24003220 doi:10.1074/jbc.M113.473348
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