Homework #8
 

1)      MDM2, an oncoprotein, is an inhibitor of p53 and is observed to be overexpressed in about 7% of human cancers. In sarcomas, the frequency of MDM2 overexpression is 20%. MDM2 belongs to a class of proteins known as E3 ligases.  MDM2 transfers the small protein ubiquitin onto p53, which tags p53 for destruction by the 26S proteasome.  An analysis of the conserved regions of MDM2 assists scientists to uncover regions that are critical for ubiquitin transfer activity. Obtain the following protein sequences from any public database you wish and align using CLUSTALW program. The protein sequences are: Human MDM2, Chimpanzee MDM2, Murine MDM2, Xenopus MDM2 and Zebrafish MDM2. Use the longest wild-type proteins sequences available for your comparisons. Give amino acid ranges of two areas that are conserved amongst these orthologs. Use the human MDM2 amino acid numbers to report on your ranges.  According to the alignment score table, which pairwise alignment has the highest score? Perform CLUSTALW again using only Human MDM2 and Zebrafish MDM2 sequences. Does the human/zebrafish alignment in this output, differ from the human/zebrafish alignment obtained in the first output? Explain.


 
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