1IYH

Crystal structure of hematopoietic prostaglandin D synthase

Summary for 1IYH

• Entry DOI: 10.2210/pdb1iyh/pdb
• Related: 1IYI
• Descriptor: HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE, MAGNESIUM ION, GLUTATHIONE, ... (4 entities in total)
• Functional Keywords: hematopoietic prostaglandin d synthase, pgds, gst, sigma-class gst, ligase, isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O60760
• Total number of polymer chains: 4
• Total formula weight: 94304.82

Authors

Inoue, T. (deposition date: 2002-08-26, release date: 2003-04-08, Last modification date: 2023-12-27)

Primary citation

Inoue, T.,Irikura, D.,Okazaki, N.,Kinugasa, S.,Matsumura, H.,Uodome, N.,Yamamoto, M.,Kumasaka, T.,Miyano, M.,Kai, Y.,Urade, Y.
Mechanism of metal activation of human hematopoietic prostaglandin D synthase
NAT.STRUCT.BIOL., 10:291-296, 2003

PubMed Abstract: Here we report the crystal structures of human hematopoietic prostaglandin (PG) D synthase bound to glutathione (GSH) and Ca2+ or Mg2+. Using GSH as a cofactor, prostaglandin D synthase catalyzes the isomerization of PGH2 to PGD2, a mediator for allergy response. The enzyme is a homodimer, and Ca2+ or Mg2+ increases its activity to approximately 150% of the basal level, with half maximum effective concentrations of 400 microM for Ca2+ and 50 microM for Mg2+. In the Mg2+-bound form, the ion is octahedrally coordinated by six water molecules at the dimer interface. The water molecules are surrounded by pairs of Asp93, Asp96 and Asp97 from each subunit. Ca(2+) is coordinated by five water molecules and an Asp96 from one subunit. The Asp96 residue in the Ca2+-bound form makes hydrogen bonds with two guanidium nitrogen atoms of Arg14 in the GSH-binding pocket. Mg2+ alters the coordinating water structure and reduces one hydrogen bond between Asp96 and Arg14, thereby changing the interaction between Arg14 and GSH. This effect explains a four-fold reduction in the K(m) of the enzyme for GSH. The structure provides insights into how Ca2+ or Mg2+ binding activates human hematopoietic PGD synthase.

PubMed: 12627223
DOI: 10.1038/nsb907

Experimental method

X-RAY DIFFRACTION (1.7 Å)