View source for 1pjz


==Solution structure of thiopurine methyltransferase from Pseudomonas syringae==
<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].
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas syringae pv. pisi]]
[[Category: Hodsdon ME]]
[[Category: Lolis E]]
[[Category: Scheuermann TH]]