TY - JOUR
T1 - Catalytic residues of group VIB calcium-independent phospholipase A 2 (iPLA2γ)
AU - Tanaka, Haruki
AU - Minakami, Reiko
AU - Kanaya, Hideki
AU - Sumimoto, Hideki
N1 - Funding Information:
We thank Professor Daisuke Kohda (Kyushu University) for helpful discussion. This work was supported in part by Grants-in-Aid for Scientific Research and National Project on Protein Structural and Functional Analyses from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by CREST of JST (Japan Science and Technology Agency) and BIRD of JST.
PY - 2004/8/6
Y1 - 2004/8/6
N2 - Although human group VIB calcium-independent phospholipase A2 (iPLA2γ) contains the lipase-consensus sequence Gly-Xaa-Ser-Xaa-Gly in the C-terminal half, its overall sequence exhibits a week similarity to those of other PLA2s, and thus no information on the catalytic site has been available. Here we show that the C-terminal region of human iPLA2γ is responsible for the enzymatic activity. Comparison of this catalytic domain with those of the mouse homologue, human cytosolic PLA2 (cPLA2), and the plant PLA2 patatin reveals that an amino acid sequence of a short segment around Asp-627 of iPLA2γ is conserved among these PLA2s, in addition to the Ser-483-containing lipase motif; the corresponding serine and aspartate in cPLA2 and patatin are known to form a catalytic dyad. Since substitution of alanine for either Ser-483 or Asp-627 results in a loss of the PLA2 activity, we propose that Ser-483 and Asp-627 of human iPLA 2γ constitute an active site similar to the Ser-Asp dyad in cPLA2 and patatin.
AB - Although human group VIB calcium-independent phospholipase A2 (iPLA2γ) contains the lipase-consensus sequence Gly-Xaa-Ser-Xaa-Gly in the C-terminal half, its overall sequence exhibits a week similarity to those of other PLA2s, and thus no information on the catalytic site has been available. Here we show that the C-terminal region of human iPLA2γ is responsible for the enzymatic activity. Comparison of this catalytic domain with those of the mouse homologue, human cytosolic PLA2 (cPLA2), and the plant PLA2 patatin reveals that an amino acid sequence of a short segment around Asp-627 of iPLA2γ is conserved among these PLA2s, in addition to the Ser-483-containing lipase motif; the corresponding serine and aspartate in cPLA2 and patatin are known to form a catalytic dyad. Since substitution of alanine for either Ser-483 or Asp-627 results in a loss of the PLA2 activity, we propose that Ser-483 and Asp-627 of human iPLA 2γ constitute an active site similar to the Ser-Asp dyad in cPLA2 and patatin.
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U2 - 10.1016/j.bbrc.2004.05.225
DO - 10.1016/j.bbrc.2004.05.225
M3 - Article
C2 - 15249229
AN - SCOPUS:3142677211
SN - 0006-291X
VL - 320
SP - 1284
EP - 1290
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -