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Old fold in a new X‐ray diffraction dataset? Low‐resolution molecular replacement using representative structural templates can provide phase information
Author(s) -
Rajavel M.,
Warrier Thulasi,
Gopal B.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21000
Subject(s) - structural genomics , triosephosphate isomerase , protein data bank , computational biology , template , structural motif , genomics , molecular replacement , computer science , crystallography , protein structure , chemistry , biology , nanotechnology , materials science , genome , gene , genetics , crystal structure , biochemistry
The advent of structural genomics has led to a dramatic increase in the number of structures deposited in the Protein Data Bank. The number of new folds, however, still remains a very small fraction of the total number of deposited structures. Recent data on the progress of the structural genomics initiative reveals that more than 85% of target proteins that progress to the stage of data collection and structure determination have a known fold. Enzymes, which tend to exploit reaction space while adopting a common stable scaffold, contribute significantly to this observation. Herein, we evaluate a method to examine the “old fold in a new dataset” scenario likely to be encountered in the structural genomics pipeline. We demonstrate that a fold detection strategy based on secondary structure signatures followed by molecular replacement using a minimalist model can be effectively used to solve the phase problem in X‐ray crystallography without further recourse to heavy atom derivatives or multiple anomalous dispersion techniques. Three common folds—the triosephosphate isomerase (TIM), adenine nucleotide alpha hydrolase‐like (HUP), and RNA recognition motif (RRM)—were examined using this approach. The results presented herein also provide an estimate of the extent of phase information that can be derived from a single domain in a large multidomain structure. Proteins 2006. © 2006 Wiley‐Liss, Inc.