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05-Exploring Sequence

05-Exploring Sequence - Exploring Sequences Members of a...

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Exploring Sequences Members of a molecular family share common features. Family resemblances are most easily detected by comparing 3D structures. Ribonuclease from cow and human are similar. This similarity is inferred by the similarity of function, and therefore expected. Suprisingly, angiogenin, a protein responsible for stimulating the growth of new blood vessels, also is structurally similar to ribonucleases based on 3D structure. Evolutionarily, ribonuclease and angiogenin must have a common ancestor at an earlier stage. 3D structures are determined for limited number (25,000) of proteins in comparison to sequences. Sequence comparison has become a powerful tool in biochemistry. Sequence databases can be searched for matches to newly elucidated sequence to provide insight into structure and function. When 3D structures are available, they can be compared to confirm relationships, and to reveal relationships undetected by sequence comparison. Evolution relationships are manifested in amino acid sequences. Bovine ribonuclease and angiogenin have identical 35% of amino acids.
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Protein Data Bank High resolution structures (atomic resolution) solved by either NMR or crystallography are deposited in the Protein Data Bank (www.pdb.org). The rate of structure solving has increased. The number of new folds discovered annually appears to have peaked. 0 500 1000 1500 2000 2500 3000 3500 4000 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 Protein Data Bank Statistics New Folds Discovered Total Folds Folds 0 5000 1 10 4 1.5 10 4 2 10 4 2.5 10 4 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 Protein Data Bank Statistics Deposited Structures Total Structures Structures
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Homologs, Paralogs, and Orthologs Homologs: molecules which have been derived from a common ancestor (homologous). Two types of homologs: Paralogs: homologs present in one species, often different in their biological function. Orthologs: homologs that are present in different species, but have very similar or identical function. Homology is often manifested by significant similarity in nucleotide or amino acid sequence and almost always manifested in 3D structure.
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Sequence Alignment Comparison of protein sequence is more effective than nucleic acid sequence because there are 20 amino acids and only 4 nucleotides. Globins: Myoglobin is a protein that binds oxygen in the muscle. Hemoglobin is the oxygen carrier protein in the blood, with four subunits ( α 2 β 2 ). Both proteins have a heme group, an iron- containing organic that binds oxygen.
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