|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of Mutant S12T of Adenosine/Methylthioadenosine Phosphorylase from Schistosoma mansoni in complex with Methylthioadenosine== | | ==Crystal structure of Mutant S12T of Adenosine/Methylthioadenosine Phosphorylase from Schistosoma mansoni in complex with Methylthioadenosine== |
| - | <StructureSection load='5f76' size='340' side='right' caption='[[5f76]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='5f76' size='340' side='right'caption='[[5f76]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5f76]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F76 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5f76]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F76 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</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]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l6i|4l6i]], [[4l5a|4l5a]], [[4l5c|4l5c]], [[4l5y|4l5y]], [[5f73|5f73]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/S-methyl-5'-thioadenosine_phosphorylase S-methyl-5'-thioadenosine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.28 2.4.2.28] </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=5f76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f76 OCA], [https://pdbe.org/5f76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f76 RCSB], [https://www.ebi.ac.uk/pdbsum/5f76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f76 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=5f76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f76 OCA], [http://pdbe.org/5f76 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f76 RCSB], [http://www.ebi.ac.uk/pdbsum/5f76 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f76 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/I0B503_SCHMA I0B503_SCHMA]] Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates (By similarity).[HAMAP-Rule:MF_03155] | + | [https://www.uniprot.org/uniprot/I0B503_SCHMA I0B503_SCHMA] Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates (By similarity).[HAMAP-Rule:MF_03155] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Blood fluke]] | + | [[Category: Large Structures]] |
| - | [[Category: S-methyl-5'-thioadenosine phosphorylase]] | + | [[Category: Schistosoma mansoni]] |
| - | [[Category: Brandao-Neto, J]] | + | [[Category: Brandao-Neto J]] |
| - | [[Category: DeMarco, R]] | + | [[Category: DeMarco R]] |
| - | [[Category: Pereira, H M]] | + | [[Category: Pereira HM]] |
| - | [[Category: Torini, J R.S]] | + | [[Category: Torini JRS]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
I0B503_SCHMA Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates (By similarity).[HAMAP-Rule:MF_03155]
Publication Abstract from PubMed
Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5 -deoxy-5 -methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity.
Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5'-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway.,Torini JR, Brandao-Neto J, DeMarco R, Pereira HD PLoS Negl Trop Dis. 2016 Dec 9;10(12):e0005178. doi:, 10.1371/journal.pntd.0005178. eCollection 2016 Dec. PMID:27935959[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Torini JR, Brandao-Neto J, DeMarco R, Pereira HD. Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5'-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway. PLoS Negl Trop Dis. 2016 Dec 9;10(12):e0005178. doi:, 10.1371/journal.pntd.0005178. eCollection 2016 Dec. PMID:27935959 doi:http://dx.doi.org/10.1371/journal.pntd.0005178
|
