title: Evolutionary information hidden in a single protein structure.
abstract: The knowledge of conserved sequences in proteins is valuable in identifying functionally or structurally important residues. Generating the conservation profile of a sequence requires aligning families of homologous sequences and having knowledge of their evolutionary relationships. Here, we report that the conservation profile at the residue level can be quantitatively derived from a single protein structure with only backbone information. We found that the reciprocal packing density profiles of protein structures closely resemble their sequence conservation profiles. For a set of 554 nonhomologous enzymes, 74% (408/554) of the proteins have a correlation coefficient > 0.5 between these two profiles. Our results indicate that the three-dimensional structure, instead of being a mere scaffold for positioning amino acid residues, exerts such strong evolutionary constraints on the residues of the protein that its profile of sequence conservation essentially reflects that of its structural characteristics.
authors.affiliation: Institute of Bioinformatics, National Chiao Tung University, HsinChu 30050, Taiwan, Republic of China.
authors.forename: Chien-Hua
authors.initials: CH
authors.lastname: Shih
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Chang
authors.forename: Yeong-Shin
authors.initials: YS
authors.lastname: Lin
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Lo
authors.forename: Jenn-Kang
authors.initials: JK
authors.lastname: Hwang
mesh_terms: D020134:Catalytic Domain; D017124:Conserved Sequence; D030562:Databases, Protein; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics*; D019143:Evolution, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004798:Enzymes; D021122:Protein Subunits