1POA

INTERFACIAL CATALYSIS: THE MECHANISM OF PHOSPHOLIPASE A2

Summary for 1POA

• Entry DOI: 10.2210/pdb1poa/pdb
• Descriptor: PHOSPHOLIPASE A2, CALCIUM ION (3 entities in total)
• Functional Keywords: hydrolase
• Biological source: Naja atra (Chinese cobra)
• Total number of polymer chains: 1
• Total formula weight: 13234.80

Authors

Scott, D.L.,Otwinowski, Z.,Sigler, P.B. (deposition date: 1992-09-07, release date: 1993-10-31, Last modification date: 2024-10-23)

Primary citation

Scott, D.L.,White, S.P.,Otwinowski, Z.,Yuan, W.,Gelb, M.H.,Sigler, P.B.
Interfacial catalysis: the mechanism of phospholipase A2.
Science, 250:1541-1546, 1990

PubMed 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.

PubMed: 2274785

Experimental method

X-RAY DIFFRACTION (1.5 Å)