Computational Genomics, November 9, 2006

Challenging Problems

Many of these excercises can done be using programs on the FASTA or BLAST WWW pages. I especially encourage you to use the PSI-SEARCH program to confirm the statistical significance of matches.

  1. Starting with the C-terminal 25% of human brc1_human, re-discover the BRCT domain involved in P53-binding. Koonin et al., (1996) Nature Genet. 13:266-268, Bork et al., (1997) FEBS Lett. 11:68-76

  2. Is the secretin receptor (scrc_human) related to the much larger class of G-protein coupled receptors that includes the beta adrenergic receptor b2ar_rat (/ecg/data/b2ar_rat.aa) and opsin opsd_human (/ecg/data/opsd_human.aa)?

    1. Identify glutamate dehydrogenase (dhe4_human) homologs in Methanococcus jannaschii and Synechocystis.

    2. Is there a yeast, C. elegans, or bacterial homologue of p53_human? What is the most distant p53-homologue that you can identify?

  4. Three proteins, hexokinase (1hkb,hxkb_yeast), actin (1atn) and HSP70 (DnaK, 1dkg) share statistically significant structural similarity (www.ebi.ac.uk/dali). Try to link the members of these three families using sequence comparison alone.

  5. Demonstrate, if possible, that S. griseus protease A prta_strgr is homologous to bovine trypsin (try1_bovin) based on sequence similarity alone.

  6. Identify homologues to the intein (protein intron) sequence in rpoa1_metja, residues 461-911.

  7. Characterize the hypothetical human proteins: NP_110444 and NP_079162

  8. Are metaxin mtx2_human and/or yqjg_ecoli glutathione transferase homologs?

  9. The current literature describes the MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism, [ref]) family of glutathione transferases, which includes MGST1_HUMAN, (MGST3_HUMAN), and MGST3_HUMAN. The MGST1 protein shares strong similarity with with Prostaglandin E synthase ( PTGES_HUMAN), while MGST2/3 share strong similarity with 5-lipoxygenase activating protein (FLAP_HUMAN) and leukotriene C4 synthase (LTC4S_HUMAN). Consider the evidence that MGST1/PGTES is homologous to MGST2,3/FLAP/LTC4S. Is this one glutathione transferase family, or two?

  10. According to Interpro, the protein O63619_BALCA contains domains that are both homologous to NADH Ubiquinone oxidoreductases (PF01059, PF00361) and aspartic lyases . Evaluate the possibility that the ammonia lyase domain is found in ubiquinone reductase.

Assignments of homology should be supported by statistically significant similarity scores and by PRSS shuffling. In cases where the assignment is based on a PSI-BLAST consensus, construct a series of single sequence links. Do not rely on protein domain database assignments alone.

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