2h11: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2h11]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H11 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H11 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2h11]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H11 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H11 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene><br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thiopurine_S-methyltransferase Thiopurine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.67 2.1.1.67] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thiopurine_S-methyltransferase Thiopurine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.67 2.1.1.67] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h11 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2h11 RCSB], [http://www.ebi.ac.uk/pdbsum/2h11 PDBsum]</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=2h11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h11 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2h11 RCSB], [http://www.ebi.ac.uk/pdbsum/2h11 PDBsum]</span></td></tr>
<table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/TPMT_HUMAN TPMT_HUMAN]] Defects in TPMT are the cause of thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:[http://omim.org/entry/610460 610460]]. TPMT is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosupressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus.  
[[http://www.uniprot.org/uniprot/TPMT_HUMAN TPMT_HUMAN]] Defects in TPMT are the cause of thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:[http://omim.org/entry/610460 610460]]. TPMT is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosupressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus.  
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Thiopurine S-methyltransferase]]
[[Category: Thiopurine S-methyltransferase]]
[[Category: Cheng, X.]]
[[Category: Cheng, X]]
[[Category: Horton, J R.]]
[[Category: Horton, J R]]
[[Category: Binary protein-cofactor complex]]
[[Category: Binary protein-cofactor complex]]
[[Category: Transferase]]
[[Category: Transferase]]

Revision as of 12:12, 16 January 2015

Amino-terminal Truncated Thiopurine S-Methyltransferase Complexed with S-Adenosyl-L-HomocysteineAmino-terminal Truncated Thiopurine S-Methyltransferase Complexed with S-Adenosyl-L-Homocysteine

Structural highlights

2h11 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Gene:TPMT (Homo sapiens)
Activity:Thiopurine S-methyltransferase, with EC number 2.1.1.67
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[TPMT_HUMAN] Defects in TPMT are the cause of thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:610460]. TPMT is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosupressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus.

Function

[TPMT_HUMAN] Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. Peng Y, Feng Q, Wilk D, Adjei AA, Salavaggione OE, Weinshilboum RM, Yee VC. Structural basis of substrate recognition in thiopurine s-methyltransferase. Biochemistry. 2008 Jun 10;47(23):6216-25. Epub 2008 May 17. PMID:18484748 doi:10.1021/bi800102x

2h11, resolution 1.89Å

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