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PDB:1POD

Protein Name

Phospholipase A2

Species

Homo sapiens (human)

Biological Context

Prostaglandins, signals of inflammation, are derived from phospholipids through synthesis by the protein prostaglandin synthase. They do however not use phospholipids directly. A precursor step on the way to synthesis of prostaglandin and related compound is carried out by phospholipase A2, an enzyme that converts membrane phospholipids into arachidonic acid (AA). AA is used by prostaglandin H2 synthase as a substrate. Phospholipase thus is an important step on the way to inflammation and inhibiting the activity of phospholipase should be a good way to deal with inflammation. The structure of the protein has been determined to understand how the enzyme acts and to serve as a starting point for structure-based drug design.

Structure Description

1pod1pod_x1pod_y

The structure of phospholipase A2 is dominated by three alpha-helices, two of them connected by an intermediate antiparallel beta sheet. For enzymatic activity the short alpha-helix at the beginning of the amino acid sequence seems to be important. The structure shown here does not contain any inhibitors, but the structure of the enzyme with a transition- state analog has also been studied. Enzyme action, from substrate to product, usually involves intermediate steps, called transition states. A transition state analog is a compound that is similar to the shape of the substrate in such an intermediate step. In this study it was observed that the first alpha-helix moves when the analog was bound.

Protein Data Bank (PDB)

References

Source

  • Scott, D.L. White, S.P. Browning, J.L. Rosa, J.J. Gelb, M.H. Sigler, P.B.;"Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudate."; Science; (1991) 254:1007-1010 PubMed:1948070.

Others

author: Arno Paehler


Japanese version:PDB:1POD