Penem and penam sulfones and their reaction mechanisms.

<p>(A) Chemical structures of penem and penam sulfone compounds. (B) proposed inhibition mechanism by a penem <b>1</b> (based on Knox’s work and others) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049035#pone.0049035-Nukaga1" target="_blank">[10]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049035#pone.0049035-Venkatesan1" target="_blank">[11]</a>; carbon atoms labeled with * are the stereo centers; (C) proposed reaction mechanism of SA1-204.</p

Data collection and refinement statistics.

a<p>Numbers in parentheses refer to the highest resolution shell.</p>b<p>rmsd, root-mean-square deviation.</p

Electron density maps showing inhibitor density in SHV-1 active site (A) Left figure is the unbiased omit <i>F</i>o-<i>F</i>c map contoured at 3.0σ of SHV-1: penem 1 complex (B) anomalous difference Fourier map contoured at 3.5σ showing strong density peaks on top of the two sulfur atoms of penem 1 intermediate; (C) Unbiased omit <i>F</i>o-<i>F</i>c map contoured at 2.5σ of SHV-1:SA1-204 complex.

<p>(D) Unbiased omit <i>F</i>o-<i>F</i>c map contoured at 3σ of SHV-1:SA3-53 complex.</p

Penam sulfone interactions in SHV-1 active site.

<p>(A) Stereo view of SA1-204 bound to SHV-1. (B) Stereo view of SA3-53 bound to SHV-1.</p

Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.

<p>Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.</p

Penem 1 in SHV-1 active site. (

<p>A) Stereo view of penem <b>1</b> interactions in SHV-1 active site. Hydrogen bonds are shown as dashed lines. (B) Stereo view of superpositioning of penem <b>1</b>:SHV-1 (black) and penem <b>2</b>:SHV-1 structures (grey). (C) Stereo view of superpositioning of penem <b>1</b>:SHV-1 (black) and penem <b>2</b>:GC1 β-lactamase (grey).</p

Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), SA1-204, and LN1-255.

<p>Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), SA1-204, and LN1-255.</p

Structure superpositioning of penam sulfone complexes.

<p>(A) Superpositioning of SA1-204:SHV-1 (black) and apo <i>wt</i> SHV-1 (grey). (B) Superpositioning of SA1-204:SHV-1 (black) and SA3-53:SHV-1 (grey). (C) Superpositioning of SA1-204:SHV-1 (black) and LN1-255:SHV-1 (grey). (D) Superpositioning of SA3-53:SHV-1 (black) and SA3-53:OXA-24 (grey, PDBid 3FZC). The following atoms are used for superpositioning: SHV-1 residues 68–77, 232–237, 128–134, 243–245 were superpositioned onto OXA-24 residues 79–88, 216–221, 126–132, and 229–231, respectively. This yielded a r.m.s.d. 0.536 Å for 26Cα atoms.</p