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Science 8 May 1987:
Vol. 236. no. 4802, pp. 694 - 701
DOI: 10.1126/science.3107125
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Articles

Science, Vol 236, Issue 4802, 694-701
Copyright © 1987 by American Association for the Advancement of Science

articles

Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution

O Herzberg and J Moult

beta-lactamases are enzymes that protect bacteria from the lethal effects of beta-lactam antibiotics, and are therefore of considerable clinical importance. The crystal structure of beta-lactamase from the Gram-positive bacterium Staphylococcus aureus PC1 has been determined at 2.5 angstrom resolution. It reveals a molecule of novel topology, made up of two closely associated domains. The active site is located at the interface between the domains, with the key catalytic residue Ser70 at the amino terminus of a buried helix. Examination of the disposition of the functionally important residues within the active site depression leads to a model for the binding of a substrate and a functional analogy to the serine proteases. The unusual topology of the secondary structure units is relevant to questions concerning the evolutionary relation to the beta-lactam target enzymes of the bacterial cell wall.


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