4i15

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==Crystal structure of TbrPDEB1==
==Crystal structure of TbrPDEB1==
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<StructureSection load='4i15' size='340' side='right' caption='[[4i15]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
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<StructureSection load='4i15' size='340' side='right'caption='[[4i15]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4i15]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I15 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I15 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4i15]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I15 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDEB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4i15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i15 OCA], [http://pdbe.org/4i15 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i15 RCSB], [http://www.ebi.ac.uk/pdbsum/4i15 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i15 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i15 OCA], [https://pdbe.org/4i15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i15 RCSB], [https://www.ebi.ac.uk/pdbsum/4i15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i15 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q8WQX9_9TRYP Q8WQX9_9TRYP]
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Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal structure of the catalytic domain of the unliganded TbrPDEB1 and its use for the in silico screening for new TbrPDEB1 inhibitors with novel scaffolds. The TbrPDEB1 crystal structure shows the characteristic folds of human PDE enzymes but also contains the parasite-specific P-pocket found in the structures of Leishmania major PDEB1 and Trypanosoma cruzi PDEC. The unliganded TbrPDEB1 X-ray structure was subjected to a structure-based in silico screening approach that combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. This approach identified six novel TbrPDEB1 inhibitors with IC50 values of 10-80 muM, which may be further optimized as potential selective TbrPDEB inhibitors.
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Discovery of Novel Trypanosoma brucei Phosphodiesterase B1 Inhibitors by Virtual Screening against the Unliganded TbrPDEB1 Crystal Structure.,Jansen C, Wang H, Kooistra AJ, de Graaf C, Orrling KM, Tenor H, Seebeck T, Bailey D, de Esch IJ, Ke H, Leurs R J Med Chem. 2013 Mar 1. PMID:23409953<ref>PMID:23409953</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4i15" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Phosphodiesterase|Phosphodiesterase]]
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Ke, H]]
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[[Category: Large Structures]]
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[[Category: Wang, H]]
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[[Category: Trypanosoma brucei]]
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[[Category: African trypanosomiasis]]
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[[Category: Ke H]]
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[[Category: Hydrolase]]
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[[Category: Wang H]]
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[[Category: Parasite pde]]
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[[Category: Sleeping sickness]]
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Crystal structure of TbrPDEB1

PDB ID 4i15

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