Fig. 4

Comparison of the active site and potential membrane interaction regions. (A) Comparison of the predicted Mg2 + -binding site in human delta-INPP5K-cd (green) with INPP5B (PDB: 4CML, gray), OCRL (PDB: 4CMN, purple), SHIP2 (PDB: 5OKM, orange), and INPP5E (PDB: 2XSW, magenta). Key residues are shown as sticks. (B) Comparison of the catalytic site residues between delta-INPP5K-cd (green) and INPP5B (gray). (C) Both the inositol-ring interaction loop involving Pro152 and His153 and the 1-phospate interaction loop involving Asn128 and Lys129 were found to be substantially shifted. Superimposition onto INPP5B indicated that the two loops are displaced from their original position, as shown for INPP5B (red dotted arrows). (D) Comparison of potential lipid interaction motifs (LC1R and LC2R). View rotated approximately 30 degrees vertically. The amino acid residues of LC1R and LC2R in INPP5B are shown in pink, and the amino acid residues of LC2R in INPP5K are shown in magenta. The amino acid residues of LC1R are invisible between Ile59 and Asn69. PtdIns-3,4-P2 is depicted as stick model with carbon atoms in pale blue, phosphorus atoms in orange, and oxygen atoms in red.