8BTV
Structure of D179N BlaC from Mycobacterium tuberculosis bound to the trans-enamine adduct of sulbactam
Summary for 8BTV
| Entry DOI | 10.2210/pdb8btv/pdb |
| Descriptor | Beta-lactamase, TRANS-ENAMINE INTERMEDIATE OF SULBACTAM, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Total number of polymer chains | 1 |
| Total formula weight | 28938.18 |
| Authors | Chikunova, A.,Bruenle, S.,Ubbink, M. (deposition date: 2022-12-02, release date: 2023-07-05, Last modification date: 2024-11-13) |
| Primary citation | van Alen, I.,Chikunova, A.,van Zanten, D.B.,de Block, A.A.,Timmer, M.,Brunle, S.,Ubbink, M. Asp179 in the class A beta-lactamase from Mycobacterium tuberculosis is a conserved yet not essential residue due to epistasis. Febs J., 290:4933-4949, 2023 Cited by PubMed Abstract: Conserved residues are often considered essential for function, and substitutions in such residues are expected to have a negative influence on the properties of a protein. However, mutations in a few highly conserved residues of the β-lactamase from Mycobacterium tuberculosis, BlaC, were shown to have no or only limited negative effect on the enzyme. One such mutant, D179N, even conveyed increased ceftazidime resistance upon bacterial cells, while displaying good activity against penicillins. The crystal structures of BlaC D179N in resting state and in complex with sulbactam reveal subtle structural changes in the Ω-loop as compared to the structure of wild-type BlaC. Introducing this mutation in four other β-lactamases, CTX-M-14, KPC-2, NMC-A and TEM-1, resulted in decreased antibiotic resistance for penicillins and meropenem. The results demonstrate that the Asp in position 179 is generally essential for class A β-lactamases but not for BlaC, which can be explained by the importance of the interaction with the side chain of Arg164 that is absent in BlaC. It is concluded that Asp179 though conserved is not essential in BlaC, as a consequence of epistasis. PubMed: 37335937DOI: 10.1111/febs.16892 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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