Correlated mutation analyses on super-family alignments reveal functionally important residues. Export

@article{citeulike:4191911, abstract = {Correlated mutation analyses (CMA) on multiple sequence alignments are widely used for the prediction of the function of amino acids. The accuracy of CMA-based predictions is mainly determined by the number of sequences, by their evolutionary distances, and by the quality of the alignments. These criteria are best met in structure-based sequence alignments of large super-families. So far, CMA-techniques have mainly been employed to study the receptor interactions. The present work shows how a novel CMA tool, called Comulator, can be used to determine networks of functionally related residues in enzymes. These analyses provide leads for protein engineering studies that are directed towards modification of enzyme specificity or activity. As proof of concept, Comulator has been applied to four enzyme super-families: the isocitrate lyase/phoshoenol-pyruvate mutase super-family, the hexokinase super-family, the RmlC-like cupin super-family, and the FAD-linked oxidases super-family. In each of those cases networks of functionally related residue positions were discovered that upon mutation influenced enzyme specificity and/or activity as predicted. We conclude that CMA is a powerful tool for redesigning enzyme activity and selectivity.}, address = {Centre of Molecular and Biomolecular Informatics, Radboud University, Nijmegen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands; Laboratory of Biochemistry, Wageningen University, Wageningen, The Netherlands}, author = {Kuipers, Remko K. and Joosten, Henk-Jan J. and Verwiel, Eugene and Paans, Sjoerd and Akerboom, Jasper and van der Oost, John and Leferink, Nicole G. and van Berkel, Willem J. and Vriend, Gert and Schaap, Peter J.}, citeulike-article-id = {4191911}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/prot.22374}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19274741}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19274741}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/121645116/ABSTRACT}, day = {15}, doi = {10.1002/prot.22374}, issn = {1097-0134}, journal = {Proteins}, keywords = {bioinformatics, correlated\_mutations}, month = {August}, number = {3}, pages = {608--616}, posted-at = {2009-03-18 11:27:22}, priority = {2}, title = {Correlated mutation analyses on super-family alignments reveal functionally important residues.}, url = {http://dx.doi.org/10.1002/prot.22374}, volume = {76}, year = {2009} }

TY - JOUR ID - citeulike:4191911 L3 - citeulike-article-id:4191911 N2 - Correlated mutation analyses (CMA) on multiple sequence alignments are widely used for the prediction of the function of amino acids. The accuracy of CMA-based predictions is mainly determined by the number of sequences, by their evolutionary distances, and by the quality of the alignments. These criteria are best met in structure-based sequence alignments of large super-families. So far, CMA-techniques have mainly been employed to study the receptor interactions. The present work shows how a novel CMA tool, called Comulator, can be used to determine networks of functionally related residues in enzymes. These analyses provide leads for protein engineering studies that are directed towards modification of enzyme specificity or activity. As proof of concept, Comulator has been applied to four enzyme super-families: the isocitrate lyase/phoshoenol-pyruvate mutase super-family, the hexokinase super-family, the RmlC-like cupin super-family, and the FAD-linked oxidases super-family. In each of those cases networks of functionally related residue positions were discovered that upon mutation influenced enzyme specificity and/or activity as predicted. We conclude that CMA is a powerful tool for redesigning enzyme activity and selectivity. IS - 3 JF - Proteins SN - 1097-0134 AD - Centre of Molecular and Biomolecular Informatics, Radboud University, Nijmegen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands; Laboratory of Biochemistry, Wageningen University, Wageningen, The Netherlands EP - 616 TI - Correlated mutation analyses on super-family alignments reveal functionally important residues. VL - 76 SP - 608 KW - bioinformatics KW - correlated_mutations AU - Kuipers, Remko AU - Joosten, Henk-Jan AU - Verwiel, Eugene AU - Paans, Sjoerd AU - Akerboom, Jasper AU - van der Oost, John AU - Leferink, Nicole AU - van Berkel, Willem AU - Vriend, Gert AU - Schaap, Peter PY - 2009/08/15/ UR - http://dx.doi.org/10.1002/prot.22374 ER -