Southwestern College, 900 Otay Lakes Rd., Chula Vista, CA 91910, USA.
Mol Phylogenet Evol. 2011 Oct;61(1):212-30. doi: 10.1016/j.ympev.2011.06.005. Epub 2011 Jun 17.
The evolution of dihydrofolate reductase (DHFR) was studied through a comprehensive structural-based analysis. An amino acid sequence alignment was generated from a superposition of experimentally determined X-ray crystal structures of wild-type (wt) DHFR from the Protein Data Bank (PDB). Using this structure-based alignment of DHFR, a metric was generated for the degree of conservation at each alignment site - not only in terms of amino acid residue, but also secondary structure, and residue class. A phylogenetic tree was generated using the alignment that compared favorably with the canonical phylogeny. This structure-based alignment was used to confirm that the degree of conservation of active-site residues in terms of both sequence as well as structure was significantly greater than non-active site residues. These results can be used in helping to understand the likely future evolution of DHFR in response to novel therapies.
通过全面的结构基础分析研究了二氢叶酸还原酶 (DHFR) 的进化。从蛋白质数据库 (PDB) 中实验确定的 X 射线晶体结构的 DHFR 的叠加中生成了氨基酸序列比对。使用此基于结构的 DHFR 比对，为每个比对位置的保守程度生成了一个度量标准 - 不仅在氨基酸残基方面，而且在二级结构和残基类别方面。使用该比对生成了一个与规范系统发育相比表现良好的系统发育树。该基于结构的比对用于确认活性位点残基在序列和结构方面的保守程度明显高于非活性位点残基。这些结果可用于帮助了解 DHFR 在应对新型疗法时可能的未来进化。
