From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1pjz.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1pjz.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1pjz| PDB=1pjz | SCENE= }} | | {{STRUCTURE_1pjz| PDB=1pjz | SCENE= }} |
| | | | |
| - | '''Solution structure of thiopurine methyltransferase from Pseudomonas syringae'''
| + | ===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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14556746}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14556746 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_14556746}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| - | 1PJZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_syringae_pv._pisi Pseudomonas syringae pv. pisi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJZ OCA]. | + | 1PJZ is a [[Single protein]] structure of sequence from [http://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]. |
| | | | |
| | ==Reference== | | ==Reference== |
| Line 30: |
Line 34: |
| | [[Category: Polymorphism]] | | [[Category: Polymorphism]] |
| | [[Category: S-adenosylmethionine]] | | [[Category: S-adenosylmethionine]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:10:20 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:10:17 2008'' |
Revision as of 12:10, 29 July 2008
Template:STRUCTURE 1pjz
Solution structure of thiopurine methyltransferase from Pseudomonas syringae
Template:ABSTRACT PUBMED 14556746
About this Structure
1PJZ is a Single protein structure of sequence from Pseudomonas syringae pv. pisi. Full experimental 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
Page seeded by OCA on Tue Jul 29 15:10:17 2008
