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| | <StructureSection load='5euc' size='340' side='right'caption='[[5euc]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='5euc' size='340' side='right'caption='[[5euc]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5euc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EUC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EUC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5euc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi_strain_CL_Brener Trypanosoma cruzi strain CL Brener]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EUC FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tc00.1047053509693.70 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=353153 TRYCC])</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]] 2.65Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5euc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5euc OCA], [http://pdbe.org/5euc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5euc RCSB], [http://www.ebi.ac.uk/pdbsum/5euc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5euc ProSAT]</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=5euc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5euc OCA], [https://pdbe.org/5euc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5euc RCSB], [https://www.ebi.ac.uk/pdbsum/5euc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5euc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q4DRC4_TRYCC Q4DRC4_TRYCC] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trycc]] | + | [[Category: Trypanosoma cruzi strain CL Brener]] |
| - | [[Category: Cousido-Siah, A]] | + | [[Category: Cousido-Siah A]] |
| - | [[Category: Delfino, J M]] | + | [[Category: Delfino JM]] |
| - | [[Category: Mitschler, A]] | + | [[Category: Mitschler A]] |
| - | [[Category: Podjarny, A]] | + | [[Category: Podjarny A]] |
| - | [[Category: Santos, J]] | + | [[Category: Santos J]] |
| - | [[Category: Valsecchi, W M]] | + | [[Category: Valsecchi WM]] |
| - | [[Category: Bisphosphonate]]
| + | |
| - | [[Category: Disorder c-terminal region]]
| + | |
| - | [[Category: Enzymatic activity modulation]]
| + | |
| - | [[Category: Hprt]]
| + | |
| - | [[Category: Phosphoribosyltransferase]]
| + | |
| - | [[Category: Proteolysis]]
| + | |
| - | [[Category: Quaternary structure]]
| + | |
| - | [[Category: Reversible oligomerization]]
| + | |
| - | [[Category: Stability]]
| + | |
| - | [[Category: T. cruzi]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
Q4DRC4_TRYCC
Publication Abstract from PubMed
Hypoxanthine phosphoribosyl transferase from Trypanosoma cruzi (TcHPRT) is a critical enzyme for the survival of the parasite. This work demonstrates that the full-length form in solution adopts a stable and enzymatically active tetrameric form, exhibiting large inter-subunit surfaces. Although this protein irreversibly aggregates during unfolding, oligomerization is reversible and can be modulated by low concentrations of urea. When the C-terminal region, which is predicted as a disordered stretch, is excised by proteolysis, TcHPRT adopts a dimeric state, suggesting that the C-terminal region acts as a main guide for the quaternary arrangement. These results are in agreement with X-ray crystallographic data presented in this work. On the other hand, the C-terminal region exhibits a modulatory role on the enzyme, as attested by the enhanced activity observed for the dimeric form. Bisphosphonates act as substrate-mimetics, uncovering long-range communications among the active sites. All in all, this work contributes to establish new ways applicable to the design of novel inhibitors that could eventually result in new drugs against parasitic diseases.
The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase.,Valsecchi WM, Cousido-Siah A, Defelipe LA, Mitschler A, Podjarny A, Santos J, Delfino JM Biochim Biophys Acta. 2016 Jun;1864(6):655-66. doi: 10.1016/j.bbapap.2016.03.005., Epub 2016 Mar 10. PMID:26969784[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Valsecchi WM, Cousido-Siah A, Defelipe LA, Mitschler A, Podjarny A, Santos J, Delfino JM. The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase. Biochim Biophys Acta. 2016 Jun;1864(6):655-66. doi: 10.1016/j.bbapap.2016.03.005., Epub 2016 Mar 10. PMID:26969784 doi:http://dx.doi.org/10.1016/j.bbapap.2016.03.005
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