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dc.contributor.authorBonsor, Daniel A.
dc.contributor.authorPostel, Sandra
dc.contributor.authorPierce, Brian G.
dc.contributor.authorWang, Ningyan
dc.contributor.authorZhu, Penny
dc.contributor.authorBuonpane, Rebecca A.
dc.contributor.authorWeng, Zhiping
dc.contributor.authorKranz, David M.
dc.contributor.authorSundberg, Eric J.
dc.date2022-08-11T08:07:59.000
dc.date.accessioned2022-08-23T15:38:11Z
dc.date.available2022-08-23T15:38:11Z
dc.date.issued2011-08-12
dc.date.submitted2013-02-22
dc.identifier.citation<p>J Mol Biol. 2011 Aug 12;411(2):321-8. doi: 10.1016/j.jmb.2011.06.009. <a href="http://dx.doi.org/10.1016/j.jmb.2011.06.009">Link to article on publisher's site</a></p>
dc.identifier.issn0022-2836 (Linking)
dc.identifier.doi10.1016/j.jmb.2011.06.009
dc.identifier.pmid21689661
dc.identifier.urihttp://hdl.handle.net/20.500.14038/25882
dc.description.abstractProtein engineering is becoming increasingly important for pharmaceutical applications where controlling the specificity and affinity of engineered proteins is required to create targeted protein therapeutics. Affinity increases of several thousand-fold are now routine for a variety of protein engineering approaches, and the structural and energetic bases of affinity maturation have been investigated in a number of such cases. Previously, a 3-million-fold affinity maturation process was achieved in a protein-protein interaction composed of a variant T-cell receptor fragment and a bacterial superantigen. Here, we present the molecular basis of this affinity increase. Using X-ray crystallography, shotgun reversion/replacement scanning mutagenesis, and computational analysis, we describe, in molecular detail, a process by which extrainterfacial regions of a protein complex can be rationally manipulated to significantly improve protein engineering outcomes.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21689661&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143254/
dc.subjectBacterial Proteins
dc.subjectCrystallography, X-Ray
dc.subjectModels, Molecular
dc.subjectMutagenesis
dc.subjectMutant Proteins
dc.subjectProtein Binding
dc.subjectProtein Engineering
dc.subject*Protein Interaction Mapping
dc.subjectProtein Structure, Quaternary
dc.subjectReceptors, Antigen, T-Cell
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBioinformatics
dc.subjectComputational Biology
dc.subjectMolecular Biology
dc.subjectSystems Biology
dc.titleMolecular basis of a million-fold affinity maturation process in a protein-protein interaction
dc.typeJournal Article
dc.source.journaltitleJournal of molecular biology
dc.source.volume411
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/bioinformatics_pubs/24
dc.identifier.contextkey3761405
html.description.abstract<p>Protein engineering is becoming increasingly important for pharmaceutical applications where controlling the specificity and affinity of engineered proteins is required to create targeted protein therapeutics. Affinity increases of several thousand-fold are now routine for a variety of protein engineering approaches, and the structural and energetic bases of affinity maturation have been investigated in a number of such cases. Previously, a 3-million-fold affinity maturation process was achieved in a protein-protein interaction composed of a variant T-cell receptor fragment and a bacterial superantigen. Here, we present the molecular basis of this affinity increase. Using X-ray crystallography, shotgun reversion/replacement scanning mutagenesis, and computational analysis, we describe, in molecular detail, a process by which extrainterfacial regions of a protein complex can be rationally manipulated to significantly improve protein engineering outcomes.</p>
dc.identifier.submissionpathbioinformatics_pubs/24
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages321-8


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