PMID: 8943034Nov 26, 1996Paper

A procedure for the prediction of temperature-sensitive mutants of a globular protein based solely on the amino acid sequence

Proceedings of the National Academy of Sciences of the United States of America
Raghavan VaradarajanC Ramakrishnan

Abstract

Temperature-sensitive (Ts) mutants of a protein are an extremely powerful tool for studying protein function in vivo and in cell culture. We have devised a method to predict those residues in a protein sequence that, when appropriately mutated, are most likely to give rise to a Ts phenotype. Since substitutions of buried hydrophobic residues often result in significant destabilization of the protein, our method predicts those residues in the sequence that are likely to be buried in the protein structure. We also indicate a set of amino acid substitutions, which should be made to generate a Ts mutant of the protein. This method requires only the protein sequence. No structural information or homologous sequence information is required. This method was applied to a test data set of 30 nonhomologous protein structures from the Protein Data Bank. All of the residues predicted by the method to be > or = 95% buried were, in fact, buried in the protein crystal structure. In contrast, only 50% of all hydrophobic residues in this data set were > or = 95% buried. This method successfully predicts several known Ts and partially active mutants of T4 lysozyme, lambda repressor, gene V protein, and staphylococcal nuclease. This method also c...Continue Reading

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Citations

Sep 3, 2008·Molecular Genetics and Genomics : MGG·Katarzyna Tomala, Ryszard Korona
Oct 31, 2009·Nature Methods·Michael CostanzoCharles Boone
Jun 7, 2005·Nucleic Acids Research·Huiling Chen, Huan-Xiang Zhou
Aug 12, 2009·Plant Physiology·Luis VidaliMagdalena Bezanilla
Apr 26, 2011·Applied and Environmental Microbiology·Clarice L HarrisonJoel S Griffitts
Jun 12, 2013·Molecular and Cellular Biology·Shataparna BanerjeeUsha Vijayraghavan
Oct 12, 2010·Algorithms for Molecular Biology : AMB·Ye TianBala Krishnamoorthy
Sep 14, 2011·PloS One·Christopher S PoultneyRichard Bonneau
May 15, 2013·PloS One·Pranveer SinghRaghavan Varadarajan
Mar 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Karl E HauschildAseem Z Ansari
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ghadiyaram ChakshusmathiRaghavan Varadarajan
May 2, 2014·Nucleic Acids Research·Kuan Pern TanMallur Srivatsan Madhusudhan
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Jul 23, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Michael McMurray
Apr 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Chetana BaligaRaghavan Varadarajan
Feb 13, 2015·Molecular Biology of the Cell·Courtney R JohnsonMichael A McMurray
Nov 23, 2016·The Journal of Biological Chemistry·Nagampalli VijaykrishnaUsha Vijayraghavan
Feb 23, 2017·Antimicrobial Agents and Chemotherapy·Stephanie L KelloggChristopher J Kristich
Mar 23, 2021·Evolution; International Journal of Organic Evolution·Elizabeth S DavenportJeffry L Dudycha
Mar 8, 2019·Biochemistry·Arti TripathiRaghavan Varadarajan

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