1pjz: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="1pjz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pjz" /> '''Solution structure of thiopurine methyltrans... |
No edit summary |
||
| (15 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Solution structure of thiopurine methyltransferase from Pseudomonas syringae== | ||
In humans, the enzyme thiopurine methyltransferase (TPMT) metabolizes | <StructureSection load='1pjz' size='340' side='right'caption='[[1pjz]]' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1pjz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_syringae_pv._pisi Pseudomonas syringae pv. pisi]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PJZ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1pjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pjz OCA], [https://pdbe.org/1pjz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pjz RCSB], [https://www.ebi.ac.uk/pdbsum/1pjz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pjz ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TPMT_PSESJ TPMT_PSESJ] Involved in the biological cycling of tellurium and selenium. Tellurium resistance (Ter) mechanism. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pj/1pjz_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pjz ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In humans, the enzyme thiopurine methyltransferase (TPMT) metabolizes 6-thiopurine (6-TP) medications, including 6-thioguanine, 6-mercaptopurine and azathioprine, commonly used for immune suppression and for the treatment of hematopoietic malignancies. S-Methylation by TPMT prevents the intracellular conversion of these drugs into active 6-thioguanine nucleotides (6-TGNs). Genetic polymorphisms in the TPMT protein sequence have been associated with decreased tissue enzymatic activities and an increased risk of life-threatening myelo-suppression from standard doses of 6-TP medications. Biochemical studies have demonstrated that TPMT deficiency is primarily associated with increased degradation of the polymorphic proteins through an ubiquitylation and proteasomal-dependent pathway. We have now determined the tertiary structure of the bacterial orthologue of TPMT from Pseudomonas syringae using NMR spectroscopy. Bacterial TPMT similarly catalyzes the S-adenosylmethionine (SAM)-dependent transmethylation of 6-TPs and shares 45% similarity (33% identity) with the human enzyme. Initial studies revealed an unstructured N terminus, which was removed for structural studies and subsequently determined to be required for enzymatic activity. Despite lacking sequence similarity to any protein of known three-dimensional structure, the tertiary structure of bacterial TPMT reveals a classical SAM-dependent methyltransferase topology, consisting of a seven-stranded beta-sheet flanked by alpha-helices on both sides. However, some deviations from the consensus topology, along with multiple insertions of structural elements, are evident. A review of the many experimentally determined tertiary structures of SAM-dependent methyltransferases demonstrates that such structural deviations from the consensus topology are common and often functionally important. | |||
Tertiary structure of thiopurine methyltransferase from Pseudomonas syringae, a bacterial orthologue of a polymorphic, drug-metabolizing enzyme.,Scheuermann TH, Lolis E, Hodsdon ME J Mol Biol. 2003 Oct 24;333(3):573-85. PMID:14556746<ref>PMID:14556746</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1pjz" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas syringae pv. pisi]] | [[Category: Pseudomonas syringae pv. pisi]] | ||
[[Category: Hodsdon ME]] | |||
[[Category: Lolis E]] | |||
[[Category: Hodsdon | [[Category: Scheuermann TH]] | ||
[[Category: Lolis | |||
[[Category: Scheuermann | |||
