2bka | pdb_00002bka
CC3(TIP30)Crystal Structure
Structural highlights
Function[HTAI2_HUMAN] Oxidoreductase required for tumor suppression. NAPDH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors. May act as a redox sensor linked to transcription through regulation of nuclear import. Isoform 1 is a metastasis suppressor with proapoptotic as well as antiangiogenic properties. Isoform 2 has an antiapoptotic effect.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCC3 (TIP30) is a protein with pro-apoptotic and anti-metastatic properties. The tumor suppressor effect of CC3 has been suggested to result from inhibition of nuclear transport by binding to importin betas or by regulating transcription through interaction in a complex with co-activator independent of AF-2 function (CIA) and the c-myc gene. Previous biochemical studies indicated that CC3 has protein kinase activity, and a structural similarity to cAMP-dependent protein kinase catalytic subunit was proposed. By contrast, bioinformatics studies suggested a relationship of CC3 to the short chain dehydrogenase reductase family. To clarify details of the CC3 structural family and ligand binding properties, we have determined the crystal structure of CC3 at 1.7-A resolution. CC3 has a short chain dehydrogenase reductase fold and binding specificity for NADPH, yet it is unlikely to be normally enzymatically active because it is monomeric. These structural results, in conjunction with data from earlier mutagenesis work on the nucleotide binding motif, suggest that NADPH binding is important for the biological activity of CC3, including interaction with importins and with the CIA/c-myc system. CC3 provides an example of the adaptation of a metabolic enzyme fold to include a regulatory role, as also seen in the case of the NADH-binding co-repressor CtBP. Crystal structure of CC3 (TIP30): implications for its role as a tumor suppressor.,El Omari K, Bird LE, Nichols CE, Ren J, Stammers DK J Biol Chem. 2005 May 6;280(18):18229-36. Epub 2005 Feb 22. PMID:15728189[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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