Structure of the SHV-1 beta-lactamase

The X-ray crystallographic structure of the SHV-1 beta-lactamase has been e stablished. The enzyme crystallizes from poly(ethylene glycol) at pH 7 in s pace group P2(1)2(1)2(1) with cell dimensions a = 49.6 Angstrom, b = 55.6 A ngstrom, and c = 87.0 Angstrom. The structure was solved by the molecular r eplacement method, and the model has been refined to an R-factor of 0.18 fo r all data in the range 8.0-1.98 Angstrom resolution. Deviations of model b onds and angles from ideal values are 0.018 Angstrom and 1.8 degrees, respe ctively. Overlay of all 263 alpha-carbon atoms in the SHV-1 and TEM-1 beta- lactamases results in an rms deviation of 1.4 Angstrom. Largest deviations occur in the H10 helix (residues 218-224) and in the loops between strands in the beta-sheet. All atoms in residues 70, 73, 130, 132, 166, and 234 in the catalytic site of SHV-1 deviate only 0.23 Angstrom (rms) from atoms in TEM-1. However, the width of the substrate binding cavity in SHV-1, as meas ured from the 104-105 and 130-132 loops on one side to the 235-238 beta-str and on the other side, is 0.7-1.2 Angstrom wider than in TEM-1. A structura l analysis of the highly different affinity of SHV-1 and TEM-1 for the beta -lactamase inhibitory protein BLIP focuses on interactions involving Asp/Gl u104.