4IBX
Crystal structure of stabilized TEM-1 beta-lactamase variant v.13
Summary for 4IBX
| Entry DOI | 10.2210/pdb4ibx/pdb |
| Related | 4IBR |
| Descriptor | Beta-lactamase TEM, CALCIUM ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total) |
| Functional Keywords | tem-1 beta-lactamase, hydrolase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 5 |
| Total formula weight | 144615.82 |
| Authors | Dellus-Gur, E.,Toth-Petroczy, A.,Elias, M.,Tawfik, D.S. (deposition date: 2012-12-09, release date: 2013-04-03, Last modification date: 2024-11-20) |
| Primary citation | Dellus-Gur, E.,Toth-Petroczy, A.,Elias, M.,Tawfik, D.S. What Makes a Protein Fold Amenable to Functional Innovation? Fold Polarity and Stability Trade-offs. J.Mol.Biol., 425:2609-2621, 2013 Cited by PubMed Abstract: Protein evolvability includes two elements--robustness (or neutrality, mutations having no effect) and innovability (mutations readily inducing new functions). How are these two conflicting demands bridged? Does the ability to bridge them relate to the observation that certain folds, such as TIM barrels, accommodate numerous functions, whereas other folds support only one? Here, we hypothesize that the key to innovability is polarity--an active site composed of flexible, loosely packed loops alongside a well-separated, highly ordered scaffold. We show that highly stabilized variants of TEM-1 β-lactamase exhibit selective rigidification of the enzyme's scaffold while the active-site loops maintained their conformational plasticity. Polarity therefore results in stabilizing, compensatory mutations not trading off, but instead promoting the acquisition of new activities. Indeed, computational analysis indicates that in folds that accommodate only one function throughout evolution, for example, dihydrofolate reductase, ≥ 60% of the active-site residues belong to the scaffold. In contrast, folds associated with multiple functions such as the TIM barrel show high scaffold-active-site polarity (~20% of the active site comprises scaffold residues) and >2-fold higher rates of sequence divergence at active-site positions. Our work suggests structural measures of fold polarity that appear to be correlated with innovability, thereby providing new insights regarding protein evolution, design, and engineering. PubMed: 23542341DOI: 10.1016/j.jmb.2013.03.033 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.68 Å) |
Structure validation
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