7A5U
Structure of E37A BlaC from Mycobacterium tuberculosis
Summary for 7A5U
| Entry DOI | 10.2210/pdb7a5u/pdb |
| Descriptor | Beta-lactamase (2 entities in total) |
| Functional Keywords | blac, beta-lactamase, mycobacterium tuberculosis, hydrolase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 1 |
| Total formula weight | 29465.02 |
| Authors | Chikunova, A.,Ahmad, M.U.,Perrakis, A.,Ubbink, M. (deposition date: 2020-08-21, release date: 2021-04-14, Last modification date: 2024-01-31) |
| Primary citation | Chikunova, A.,Manley, M.P.,Ud Din Ahmad, M.,Bilman, T.,Perrakis, A.,Ubbink, M. Conserved residues Glu37 and Trp229 play an essential role in protein folding of beta-lactamase. Febs J., 288:5708-5722, 2021 Cited by PubMed Abstract: Evolutionary robustness requires that the number of highly conserved amino acid residues in proteins is minimized. In enzymes, such conservation is observed for catalytic residues but also for some residues in the second shell or even further from the active site. β-Lactamases evolve in response to changing antibiotic selection pressures and are thus expected to be evolutionarily robust, with a limited number of highly conserved amino acid residues. As part of the effort to understand the roles of conserved residues in class A β-lactamases, we investigate the reasons leading to the conservation of two amino acid residues in the β-lactamase BlaC, Glu37, and Trp229. Using site-directed mutagenesis, we have generated point mutations of these residues and observed a drastic decrease in the levels of soluble protein produced in Escherichia coli, thus abolishing completely the resistance of bacteria against β-lactam antibiotics. However, the purified proteins are structurally and kinetically very similar to the wild-type enzyme, only differing by exhibiting a slightly lower melting temperature. We conclude that conservation of Glu37 and Trp229 is solely caused by an essential role in the folding process, and we propose that during folding Glu37 primes the formation of the central β-sheet and Trp229 contributes to the hydrophobic collapse into a molten globule. ENZYME: EC 3.5.2.6. DATABASE: Structural data are available in PDB database under the accession number 7A5U. PubMed: 33792206DOI: 10.1111/febs.15854 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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