Interfacial catalysis: The mechanism of phospholipase A2

David L. Scott, Steven P. White, Zbyszek Otwinowski, Wei Yuan, Michael H. Gelb, Paul B. Sigler

Research output: Contribution to journalArticle

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Abstract

A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2s. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA 2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme's structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile.

Original languageEnglish (US)
Pages (from-to)1541-1546
Number of pages6
JournalScience
Volume250
Issue number4987
DOIs
StatePublished - Jan 1 1990

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    Scott, D. L., White, S. P., Otwinowski, Z., Yuan, W., Gelb, M. H., & Sigler, P. B. (1990). Interfacial catalysis: The mechanism of phospholipase A2. Science, 250(4987), 1541-1546. https://doi.org/10.1126/science.2274785