1lky
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1lky.jpg|left|200px]] | + | [[Image:1lky.jpg|left|200px]] |
| - | + | ||
| - | '''Structure of the wild-type TEL-SAM polymer''' | + | {{Structure |
| + | |PDB= 1lky |SIZE=350|CAPTION= <scene name='initialview01'>1lky</scene>, resolution 2.30Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Structure of the wild-type TEL-SAM polymer''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1LKY is a [ | + | 1LKY is a [[Protein complex]] structure of sequences 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=1LKY OCA]. |
==Reference== | ==Reference== | ||
| - | Native interface of the SAM domain polymer of TEL., Tran HH, Kim CA, Faham S, Siddall MC, Bowie JU, BMC Struct Biol. 2002 Aug 22;2:5. PMID:[http:// | + | Native interface of the SAM domain polymer of TEL., Tran HH, Kim CA, Faham S, Siddall MC, Bowie JU, BMC Struct Biol. 2002 Aug 22;2:5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12193272 12193272] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| Line 26: | Line 35: | ||
[[Category: tyrosine kinase]] | [[Category: tyrosine kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:32:05 2008'' |
Revision as of 10:32, 20 March 2008
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of the wild-type TEL-SAM polymer
Contents |
Overview
BACKGROUND: TEL is a transcriptional repressor containing a SAM domain that forms a helical polymer. In a number of hematologic malignancies, chromosomal translocations lead to aberrant fusions of TEL-SAM to a variety of other proteins, including many tyrosine kinases. TEL-SAM polymerization results in constitutive activation of the tyrosine kinase domains to which it becomes fused, leading to cell transformation. Thus, inhibitors of TEL-SAM self-association could abrogate transformation in these cells. In previous work, we determined the structure of a mutant TEL-SAM polymer bearing a Val to Glu substitution in center of the subunit interface. It remained unclear how much the mutation affected the architecture of the polymer, however. RESULTS: Here we determine the structure of the native polymer interface. To accomplish this goal, we introduced mutations that block polymer extension, producing a heterodimer with a wild-type interface. We find that the structure of the wild-type polymer interface is quite similar to the mutant structure determined previously. With the structure of the native interface, it is possible to evaluate the potential for developing therapeutic inhibitors of the interaction. We find that the interacting surfaces of the protein are relatively flat, containing no obvious pockets for the design of small molecule inhibitors. CONCLUSION: Our results confirm the architecture of the TEL-SAM polymer proposed previously based on a mutant structure. The fact that the interface contains no obvious potential binding pockets suggests that it may be difficult to find small molecule inhibitors to treat malignancies in this way.
Disease
Known diseases associated with this structure: Leukemia, acute myeloid, somatic OMIM:[600618]
About this Structure
1LKY is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Native interface of the SAM domain polymer of TEL., Tran HH, Kim CA, Faham S, Siddall MC, Bowie JU, BMC Struct Biol. 2002 Aug 22;2:5. PMID:12193272
Page seeded by OCA on Thu Mar 20 12:32:05 2008
