(A) The homo-tetrameric conformation of L1 MBL (PDB entry 1SML). Three monomers are illustrated in surface representation; the fourth monomer is shown in green cartoon. (B) A close up of the …
Proposed mechanism of β-lactam hydrolysis by S. maltophilia L1 MBL.
(A) Conserved secondary structure elements for the three subclasses are indicated above the sequences: α-helix, β-sheets, and L-loop. Amino acid insertions in the newly sequences enzymes are …
(A) Implied timescales (ITS) plot. The ITS plot describes the convergence behavior of the implied timescales associated with the processes at the lag time of 5 ns. (B) Net flux pathways plot …
Mean first passage time.
The CK test plot, along with the ITS plot (Figure 2A) was used to assess the Markovian behavior of the constructed model.
Structures exist in the closed, intermediate, and open states defined by a salt bridge between D150c-R236, π–π stacking interaction between H151-Y227 and the conformation of the cyclic side chain of …
The distances between the D150c-R236 salt bridge (blue), H151-Y227 π–π stacking (orange), A224-Q310 (red), and P225-Zn (green) have been illustrated.
Violin plots highlighting the calculated D150c-R236 salt bridge interaction in each of the four subunits in different metastable states.
Violin plots highlighting the calculated H151-Y227 π–π stacking interaction in each of the four subunits in different metastable states.
Violin plots highlighting the calculated P225-Zn distance in each of the four subunits in different metastable states.
Violin plots highlighting the calculated A224(bb)-Q310(sc) distance in each of the four subunits in different metastable states.
A Cα-RMSD superimposition of state 7 (green) with a monomer from apo state crystal structure (PDB id 1SML; orange; 0.79 Å) and with inhibitor complex (PDB id 5DPX; purple; 0.77 Å) structure of L1 …
CVAE-learned features of high-dimensional data represented in 2D following t-distributed stochastic neighbor embedding (tSNE) treatment. (A) The results show that A and C subunits show similar …
(A) The training and validation loss plotted as assessed simultaneously over consecutive epochs at various reduced dimensions. Dimension 14 was selected for further analysis as it displayed the …
Individual subunits are plotted on the tSNE space after clustering of states 1–7. A comparison with Figure 4 highlights the open (state 1), intermediate open (state 4), intermediate closed (state …
The cis/trans conformation of a peptide bond is determined by the torsion of the ω angle. The ω torsion angle is close to 0° in the cis configuration, or ca. 180° in the trans configuration. The ω …
(a) The training and validation loss plot as assessed over consecutive epochs at various reduced dimensions. (b) Validation loss during CVAE implementation is plotted at different latent dimensions …
(a) The training and validation loss plot as assessed over consecutive epochs at various reduced dimensions. (b) Validation loss during CVAE implementation is plotted at different latent dimensions …
(a) The training and validation loss plot as assessed over consecutive epochs at various reduced dimensions. (b) Validation loss during CVAE implementation is plotted at different latent dimensions …
(a) The training and validation loss plot as assessed over consecutive epochs at various reduced dimensions. (b) Validation loss during CVAE implementation is plotted at different latent dimensions …
α3-β7 | GGSDDLHFGDGITYPPANAD Residues 149–171 |
β12-α5 | ADSLSAPGYQLQGNPRYPH Residues 219–239 |
The reported values are the mode of at least three biological replicates.
Strain | MIC value (mg/l)* | |||||
---|---|---|---|---|---|---|
CAZ | FEP | IMI | MER | TEB | TEB + CS319† | |
DH10B pBC SK blaL1a | 256 | 2 | 16 | 16 | 32 | 2 |
DH10B pBC SK blaL1a_H151V | 2 | 0.03 | 0.125 | 0.03 | ≤0.03 | ≤0.03 |
DH10B pBC SK blaL1a_D150cV | 256 | 1 | 8 | 8 | 4 | 0.25 |
DH10B pBC SK blaL1a_P225A | 64 | 0.125 | 0.25 | 2 | 0.125 | ≤0.03 |
DH10B pBC SK blaL1a_R236A | 256 | 2 | 8 | 8 | 4 | 0.25 |
DH10B pBC SK blaL1a_Y227A | 64 | 0.25 | 0.25 | 2 | 0.5 | ≤0.03 |
CAZ, ceftazidime; FEP, cefepime; IMI, imipenem; MER, meropenem; TEB, tebipenem.
CS319 was added to a final concentration of 100 mg/l.