The Structural Basis of Aspirin Activity Inferred from the Crystal Structure of Inactivated Prostaglandin H2 Synthase

The X-Ray Crystal Structure of the Membrane Protein Prostaglandin H2 Synthase-1

COMPND
MOLECULE: PROSTAGLANDIN H2 SYNTHASE-1. ACETYLATED BY THE
ASPIRIN ANALOG 2-BROMOACETOXY BENZOIC ACID.

THE SIDE CHAIN OXYGEN OG OF SER 530 IS ESTERIFIED WITH A
2-BROMOACETYL GROUP:

|
SER 530 CH-CH2-O-CO-CH2BR
|

THIS SEQUENCE IS FOUND IN ENTRY 1PRH. THE NUMBERING IS DERIVED FROM THE PRE-PROTEIN, WHICH CONTAINS A 24-RESIDUE SIGNAL SEQUENCE WHICH IS CLEAVED DURING MATURATION.

PROSTAGLANDIN H2 SYNTHASE-1, PROTOPORPHYRIN IX CONTAINING FE, 2-BROMOACETYL GROUP, 2-HYDROXYBENZOIC ACID

MTRIX
THE TRANSFORMATION PRESENTED ON MTRIX RECORDS BELOW
DESCRIBES THE NON-CRYSTALLOGRAPHIC RELATIONSHIP TO CREATE
THE SECOND SUBUNIT OF THE PGHS-1 DIMER.