3V5M
Crystal structure of M69V mutant of SHV beta-lactamase
Summary for 3V5M
| Entry DOI | 10.2210/pdb3v5m/pdb |
| Related | 2H10 |
| Descriptor | Beta-lactamase, CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE (3 entities in total) |
| Functional Keywords | class a beta-lactamase fold, hydrolyze b-lactam antibiotics, hydrolase |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 1 |
| Total formula weight | 29892.16 |
| Authors | |
| Primary citation | Ke, W.,Rodkey, E.A.,Sampson, J.M.,Skalweit, M.J.,Sheri, A.,Pagadala, S.R.,Nottingham, M.D.,Buynak, J.D.,Bonomo, R.A.,van den Akker, F. The importance of the trans-enamine intermediate as a beta-lactamase inhibition strategy probed in inhibitor-resistant SHV beta-lactamase variants. Chemmedchem, 7:1002-1008, 2012 Cited by PubMed Abstract: The ability of bacteria to express inhibitor-resistant (IR) β-lactamases is stimulating the development of novel inhibitors of these enzymes. The 2'β-glutaroxypenicillinate sulfone, SA2-13, was previously designed to enhance the stabilization of the deacylation-refractory, trans-enamine inhibitory intermediate. To test whether this mode of inhibition can overcome different IR mutations, we determined the binding mode of SA2-13 through X-ray crystallography, obtaining co-crystals of the inhibitor-protein complex by soaking crystals of the IR sulfhydryl variable (SHV) β-lactamase variants S130G and M69V with the inhibitor. The 1.45 Å crystal structure of the S130G SHV:SA2-13 complex reveals that SA2-13 is still able to form the stable trans-enamine intermediate similar to the wild-type complex structure, yet with its carboxyl linker shifted deeper into the active site in the space vacated by the S130G mutation. In contrast, data from crystals of the M69V SHV:SA2-13 complex at 1.3 Å did not reveal clear inhibitor density indicating that this IR variant disfavors the trans-enamine conformation, likely due to a subtle shift in A237. PubMed: 22438274DOI: 10.1002/cmdc.201200006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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