2VKV
TetR (BD) variant L17G with reverse phenotype
Summary for 2VKV
| Entry DOI | 10.2210/pdb2vkv/pdb |
| Related | 1A6I 1BJ0 1BJY 1BJZ 1DU7 1ORK 1QPI 2TCT 2TRT 2VKE |
| Descriptor | TETRACYCLINE REPRESSOR PROTEIN CLASS B FROM TRANSPOSON TN10, TETRACYCLINE REPRESSOR PROTEIN CLASS D, 5A,6-ANHYDROTETRACYCLINE, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | transcription, transcription regulation, disorder to order mechanism, antibiotic resistance, helix-turn-helix motif, bacterial repressor, anhydrotetracycline, metal-binding, reverse phenotype, tetr, plasmid, repressor, magnesium, dna-binding |
| Biological source | ESCHERICHIA COLI |
| Total number of polymer chains | 1 |
| Total formula weight | 23824.53 |
| Authors | Resch, M.,Striegl, H.,Henssler, E.M.,Sevvana, M.,Egerer-Sieber, C.,Schiltz, E.,Hillen, W.,Muller, Y.A. (deposition date: 2008-01-02, release date: 2008-07-08, Last modification date: 2023-12-13) |
| Primary citation | Resch, M.,Striegl, H.,Henssler, E.M.,Sevvana, M.,Egerer-Sieber, C.,Schiltz, E.,Hillen, W.,Muller, Y.A. A Protein Functional Leap: How a Single Mutation Reverses the Function of the Transcription Regulator Tetr. Nucleic Acids Res., 36:4390-, 2008 Cited by PubMed Abstract: Today's proteome is the result of innumerous gene duplication, mutagenesis, drift and selection processes. Whereas random mutagenesis introduces predominantly only gradual changes in protein function, a case can be made that an abrupt switch in function caused by single amino acid substitutions will not only considerably further evolution but might constitute a prerequisite for the appearance of novel functionalities for which no promiscuous protein intermediates can be envisaged. Recently, tetracycline repressor (TetR) variants were identified in which binding of tetracycline triggers the repressor to associate with and not to dissociate from the operator DNA as in wild-type TetR. We investigated the origin of this activity reversal by limited proteolysis, CD spectroscopy and X-ray crystallography. We show that the TetR mutant Leu17Gly switches its function via a disorder-order mechanism that differs completely from the allosteric mechanism of wild-type TetR. Our study emphasizes how single point mutations can engender unexpected leaps in protein function thus enabling the appearance of new functionalities in proteins without the need for promiscuous intermediates. PubMed: 18587152DOI: 10.1093/NAR/GKN400 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.74 Å) |
Structure validation
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