2pbj

GSH-heme bound microsomal prostaglandin E synthase

spinqualitylabelsall models 2pbj, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2pbj is a 4 chain structure with sequence from Macaca fascicularis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: CL, GSH, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PGES2_MACFA Isomerase that catalyzes the conversion of unstable intermediate of prostaglandin E2 H2 (PGH2) into the more stable prostaglandin E2 (PGE2) form. May also have transactivation activity toward IFN-gamma (IFNG), possibly via an interaction with CEBPB; however, the relevance of transcription activation activity remains unclear. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Prostaglandin E2 synthase (PGES) catalyzes the isomerization of PGH2 to PGE2. PGES type 2 (mPGES-2) is a membrane-associated enzyme, whose N-terminal section is apparently inserted into the lipid bilayer. Both intact and N-terminal truncated enzymes have been isolated and have similar catalytic activity. The recombinant N-terminal truncated enzyme purified from Escherichia coli HB101 grown in LB medium containing delta-aminolevulinate and Fe(NO3)3 has a red color, while the same enzyme purified from the same E. coli grown in minimal medium has no color. The red-colored enzyme has been characterized by mass, fluorescence, and EPR spectroscopies and X-ray crystallography. The enzyme is found to contain bound glutathione (GSH) and heme. GSH binds to the active site with six H-bonds, while a heme is complexed with bound GSH forming a S-Fe coordination bond with no polar interaction with mPGES-2. There is a large open space between the heme and the protein, where a PGH2 might be able to bind. The heme dissociation constant is 0.53 microM, indicating that mPGES-2 has relatively strong heme affinity. Indeed, expression of mPGES-2 in E. coli stimulates heme biosynthesis. Although mPGES-2 has been reported to be a GSH-independent PGES, the crystal structure and sequence analysis indicate that mPGES-2 is a GSH-binding protein. The GSH-heme complex-bound enzyme (mPGES-2h) catalyzes formation of 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid and malondialdehyde from PGH2, but not formation of PGE2. The following kinetic parameters at 37 degrees C were determined: KM = 56 microM, kcat = 63 s-1, and kcat/KM = 1.1 x 10(6) M-1 s-1. They suggest that mPGES-2h has significant catalytic activity for PGH2 degradation. It is possible that both GSH-heme complex-free and -bound enzymes are present in the same tissues. mPGES-2 in heme-rich liver is most likely to become the form of mPGES-2h and might be involved in degradation reactions similar to that of cytochrome P450. Since mPGES-2 is an isomerase and mPGES-2h is a lyase, mPGES-2 cannot simply be classified into one of six classes set by the International Union of Biochemistry and Molecular Biology. PGH2 degradation pathway catalyzed by GSH-heme complex bound microsomal prostaglandin E2 synthase type 2: the first example of a dual-function enzyme.,Yamada T, Takusagawa F Biochemistry. 2007 Jul 17;46(28):8414-24. Epub 2007 Jun 22. PMID:17585783 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Prostaglandin E synthase

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