1pjz
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= | ||
| - | |ACTIVITY= [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] | + | |ACTIVITY= <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> |
|GENE= TPM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=59510 Pseudomonas syringae pv. pisi]) | |GENE= TPM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=59510 Pseudomonas syringae pv. pisi]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pjz OCA], [http://www.ebi.ac.uk/pdbsum/1pjz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pjz RCSB]</span> | ||
}} | }} | ||
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[[Category: s-adenosylmethionine]] | [[Category: s-adenosylmethionine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:00:47 2008'' |
Revision as of 20:00, 30 March 2008
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| Gene: | TPM (Pseudomonas syringae pv. pisi) | ||||||
| Activity: | Thiopurine S-methyltransferase, with EC number 2.1.1.67 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Solution structure of thiopurine methyltransferase from Pseudomonas syringae
Overview
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.
About this Structure
1PJZ is a Single protein structure of sequence from Pseudomonas syringae pv. pisi. Full crystallographic information is available from OCA.
Reference
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
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