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 PLA2s, 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
StatePublished - Dec 14 1990

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Cobra Venoms
Phospholipases A2
Catalysis
Bee Venoms
Enzymes
Catalytic Domain
Facilitated Diffusion
Pharmacologic Actions
Lipids
Elapidae
Organophosphonates
Fatty Acids
X-Rays
Ions
Calcium
Water

ASJC Scopus subject areas

  • General

Cite this

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.

Interfacial catalysis : The mechanism of phospholipase A2. / Scott, David L.; White, Steven P.; Otwinowski, Zbyszek; Yuan, Wei; Gelb, Michael H.; Sigler, Paul B.

In: Science, Vol. 250, No. 4987, 14.12.1990, p. 1541-1546.

Research output: Contribution to journalArticle

Scott, DL, White, SP, Otwinowski, Z, Yuan, W, Gelb, MH & Sigler, PB 1990, 'Interfacial catalysis: The mechanism of phospholipase A2', Science, vol. 250, no. 4987, pp. 1541-1546.
Scott DL, White SP, Otwinowski Z, Yuan W, Gelb MH, Sigler PB. Interfacial catalysis: The mechanism of phospholipase A2. Science. 1990 Dec 14;250(4987):1541-1546.
Scott, David L. ; White, Steven P. ; Otwinowski, Zbyszek ; Yuan, Wei ; Gelb, Michael H. ; Sigler, Paul B. / Interfacial catalysis : The mechanism of phospholipase A2. In: Science. 1990 ; Vol. 250, No. 4987. pp. 1541-1546.
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