ArticleBiochemistry2009
Structural and thermodynamic analysis of a conformationally strained circular permutant of barnase.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Design of stable circular permutants of the GroEL chaperone apical domain.Cell communication and signaling : CCS · 2024Article
- Automated and Efficient Generation of General Molecular Aggregate Structures.Angewandte Chemie (International ed. in English) · 2023Article
- Enhancing response of a protein conformational switch by using two disordered ligand binding domains.Frontiers in molecular biosciences · 2023Article
- Engineering protein activity into off-the-shelf DNA devices.Cell reports methods · 2022Article
- Engineering a Fluorescent Protein Color Switch Using Entropy-Driven β-Strand Exchange.ACS sensors · 2022Article
- Engineering protein and DNA tools for creating DNA-dependent protein switches.Methods in enzymology · 2022Article
- Circular zymogens of human ribonuclease 1.Protein science : a publication of the Protein Society · 2019Article
- Article
- Investigating the Effect of Chain Connectivity on the Folding of a Beta-Sheet Protein On and Off the Ribosome.Journal of molecular biology · 2018Article
- Construction of Allosteric Protein Switches by Alternate Frame Folding and Intermolecular Fragment Exchange.Methods in molecular biology (Clifton, N.J.) · 2017Article
- The Structure of a Thermophilic Kinase Shapes Fitness upon Random Circular Permutation.ACS synthetic biology · 2016Article
- Engineering of Yarrowia lipolytica lipase Lip8p by circular permutation to alter substrate and temperature characteristics.Journal of industrial microbiology & biotechnology · 2014Article
- A circularly permuted photoactive yellow protein as a scaffold for photoswitch design.Biochemistry · 2013Article
- Stepwise conversion of a binding protein to a fluorescent switch: application to Thermoanaerobacter tengcongensis ribose binding protein.Biochemistry · 2013Article
- Designing redox potential-controlled protein switches based on mutually exclusive proteins.Protein science : a publication of the Protein Society · 2012Article
- Article
- Crystal structure of circular permuted RoCBM21 (CP90): dimerisation and proximity of binding sites.PloS one · 2012Article
- Molecular simulations of mutually exclusive folding in a two-domain protein switch.Biophysical journal · 2011Article
- Converting a protein into a switch for biosensing and functional regulation.Protein science : a publication of the Protein Society · 2011Review
- Engineering an artificial zymogen by alternate frame protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
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Authors and funding
5 authors.
Funding
Abstract
Circular permutation of a protein covalently links its original termini and creates new ends at another location. To maintain the stability of the permuted structure, the termini are typically bridged by a peptide long enough to span the original distance between them. Here, we take the opposite approach and employ a very short linker to introduce conformational strain into a protein by forcing its termini together. We join the N- and C-termini of the small ribonuclease barnase (normally 27.2 A distant) with a single Cys residue and introduce new termini at a surface loop, to create pBn. Compared to a similar variant permuted with an 18-residue linker, permutation with a single amino acid dramatically destabilizes barnase. Surprisingly, pBn is folded at 10 degrees C and possesses near wild-type ribonuclease activity. The 2.25 A X-ray crystal structure of pBn reveals how the barnase fold is able to adapt to permutation, partially defuse conformational strain, and preserve enzymatic function. We demonstrate that strain in pBn can be relieved by cleaving the linker with a chemical reagent. Catalytic activity of both uncleaved (strained) pBn and cleaved (relaxed) pBn is proportional to their thermodynamic stabilities, i.e., the fraction of folded molecules. The stability and activity of cleaved pBn are dependent on protein concentration. At concentrations above approximately 2 microM, cleaving pBn is predicted to increase the fraction of folded molecules and thus enhance ribonuclease activity at 37 degrees C. This study suggests that introducing conformational strain by permutation, and releasing strain by cleavage, is a potential mechanism for engineering an artificial zymogen.
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