Genomic organization, characterization, and molecular 3D model of GDE1, a novel mammalian glycerophosphoinositol phosphodiesterase.
Glycerophosphodiester phosphodiesterase (GDPD) catalyzes the hydrolysis of deacylated glycerophospholipids to glycerol phosphate and alcohol. A mammalian glycerophosphoinositol phosphodiesterase, GDE1/MIR16, was recently identified as an interacting protein of the regulator of G protein signaling 16 (RGS16) providing a link between phosphoinositide metabolism and G protein signal transduction. To further understand the function and properties of human GDE1, we determined its genomic organization and its biochemical and structural characteristics. GDE1 encodes a 331-residue protein with two hydrophobic domains and contains a GDE domain that shares strong homologies with GDE1-related proteins as well as bacterial GDPDs. The human GDE1 gene is located on chromosome 16p12-p11.2 and contains six exons and five introns. A molecular 3D model, which was built based on the crystal structure of Escherichia coli GDPD (1YDY), provides the first structural information of human GDE1 and suggests a TIM barrel core as typically found in bacterial GDPDs. Furthermore, a model of the putative catalytic motif within the GDE domain was nearly identical to the corresponding domain of GDPD and highlights the individual core residues Glu97, Asp99, and His112, which are crucial to maintaining GDE1 catalytic activity. These studies provide important new insights into understanding the function of GDE1 and GDE1-related proteins.
Cancer Research Center of Hawaii, Natural Products and Cancer Biology Program, University of Hawaii at Manoa, 1236 Lauhala Street, Honolulu, HI 96813, USA. abachmann@crch.hawaii.edu
André S
AS
Bachmann
Frederick F
FF
Duennebier
Gabor
G
Mocz
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D040681:Structural Homology, Protein
D005136:Eye Proteins; D020404:Glycerophospholipids; D020710:RGS Proteins; C107413:RGS16 protein; D010727:Phosphoric Diester Hydrolases; C038133:glycerophosphodiester phosphodiesterase