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Consensus Protein Design without Phylogenetic Bias

Jäckel, Christian and Bloom, Jesse D. and Kast, Peter and Arnold, Frances H. and Hilvert, Donald (2010) Consensus Protein Design without Phylogenetic Bias. Journal of Molecular Biology, 399 (4). pp. 541-546. ISSN 0022-2836. PMCID PMC2904866. doi:10.1016/j.jmb.2010.04.039.

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Consensus design is an appealing strategy for the stabilization of proteins. It exploits amino acid conservation in sets of homologous proteins to identify likely beneficial mutations. Nevertheless, its success depends on the phylogenetic diversity of the sequence set available. Here, we show that randomization of a single protein represents a reliable alternative source of sequence diversity that is essentially free of phylogenetic bias. A small number of functional protein sequences selected from binary-patterned libraries suffice as input for the consensus design of active enzymes that are easier to produce and substantially more stable than individual members of the starting data set. Although catalytic activity correlates less consistently with sequence conservation in these extensively randomized proteins, less extreme mutagenesis strategies might be adopted in practice to augment stability while maintaining function.

Item Type:Article
Related URLs:
URLURL TypeDescription DOIArticle CentralArticle
Bloom, Jesse D.0000-0003-1267-3408
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2010 Elsevier Ltd. Received 31 January 2010; revised 20 April 2010; accepted 22 April 2010. Edited by F. Schmid. Available online 28 April 2010.
Subject Keywords:protein stabilization; multiple sequence alignments; consensus mutation; binary patterning; chorismate mutase
Issue or Number:4
PubMed Central ID:PMC2904866
Record Number:CaltechAUTHORS:20100713-090942319
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:19016
Deposited By: Tony Diaz
Deposited On:14 Jul 2010 18:36
Last Modified:08 Nov 2021 23:49

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