1pjz

<StructureSection load='1pjz' size='340' side='right'caption='[[1pjz]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[1pjz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Psesj Psesj]. 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPM ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=59510 PSESJ])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thiopurine_S-methyltransferase Thiopurine S-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.67 2.1.1.67] </span></td></tr>

[[https://www.uniprot.org/uniprot/TPMT_PSESJ TPMT_PSESJ]] Involved in the biological cycling of tellurium and selenium. Tellurium resistance (Ter) mechanism.

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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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<div class="pdbe-citations 1pjz" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Psesj]]

[[Category: Thiopurine S-methyltransferase]]

[[Category: Hodsdon, M E]]

[[Category: Lolis, E]]

[[Category: Scheuermann, T H]]

[[Category: Transferase]]