首页 | 本学科首页   官方微博 | 高级检索  
     


The pattern of amino acid replacements in alpha/beta-barrels
Authors:Dean Antony M  Neuhauser Claudia  Grenier Elise  Golding G Brian
Affiliation:The Biological Process Technology Institute, University of Minnesota, St. Paul, 55108, USA. adean@biosci.umn.edu
Abstract:The determinants of site-to-site variability in the rate of amino acid replacement in alpha/beta-barrel enzyme structures are investigated. Of 125 available alpha/beta-barrel structures, only 25 meet a variety of phylogenetic and statistical criteria necessary to ensure sufficient data for reliable analysis. These 25 enzyme structures (from a wide variety of taxa with diverse lifestyles in diverse habitats) differ greatly in size, number, and topology of domains in addition to the alpha/beta-barrel, quaternary structure, metabolic role, reaction catalyzed, presence of prosthetic groups, regulatory mechanisms, use of cofactors, and catalytic mechanisms. Yet, with the exception of ribulose-1,5-bisphosphate carboxylase, all structures have similar frequency distributions of amino acid replacement rates. Hence, site-specific variability in rates of evolution is largely independent of differences in biology, biochemistry, and molecular structure. A correlation between site-specific rate variation and (1) distance from the active site, (2) solvent accessibility, and (3) treating glycines in unusual main-chain conformations as a separate class, explains approximately half the causal variation. Secondary structure exerts little influence on the pattern and distribution of replacements. Additional domains and subunits, side-chain hydrogen bonds, unusual side-chain rotamers, nonplanar peptide bonds, strained main-chain conformations, and buried hydrophilic-charged residues contribute little to variability among sites because they are rare. Nonlinear models do not improve the fits. In several enzymes, deviations from the typical pattern of replacements suggest the possible action of natural selection. A statistical analysis shows that, in all cases, much of the remaining unexplained variation is not attributable to chance and that other, as yet unidentified, causal relations must exist.
Keywords:
本文献已被 PubMed Oxford 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号