1. Crystal Structure of a Phosphoinositide Phosphatase, MTMR2
Michael J Begley, Gregory S Taylor, Soo-A Kim, Donna M Veine, Jack E Dixon, Jeanne A Stuckey 
Molecular Cell 
Volume 12, Issue 6, Pages (December 2003)
DOI: /S (03)

2. Figure 1 Domain Structures of Myotubularin-Related Proteins
PTP, PH-GRAM, and SET-interaction domain (SID) boundaries were determined using a primary sequence alignment of the myotubularin family and the MTMR2 crystal structure. Predicted coiled-coil, FYVE, PH, and DENN domain boundaries were obtained from COILS (Lupas, 1996) and SMART (Schultz et al., 1998).
Molecular Cell  , DOI: ( /S (03) )

3. Figure 2 Crystal Structure of MTMR2
(A) Overall view of the MTMR2 structure (amino acids ). The PH-GRAM domain is shown in green, the phosphatase domain in blue, the active site motif (P-Loop) in yellow, and the linker between the two domains in orange.
(B) The minimum structural core of PTPs, defined by the crystal structure of VHR (Yuvaniyama et al., 1996), was overlayed on the MTMR2 structure and is shown in red.
(C) The SET-interaction domain (SID), corresponding to amino acids , is shown in red. The view is rotated 90° about the vertical of (A).
Molecular Cell  , DOI: ( /S (03) )

4. Figure 3
The GRAM Domain of MTMR2 Is Part of a Larger Motif with a PH Domain Fold
(A) The PH-GRAM domain of MTMR2 (residues ) is shown as a green and red ribbon. The red portion corresponds to the previously described GRAM domain (Doerks et al., 2000).
(B) The PH domain of pleckstrin (PDB entry 1PLS) is shown as a blue ribbon.
(C) Alignment of predicted GRAM domain containing proteins. Predicted GRAM domain containing proteins include MTMR2, a glycosyltransferase (L9470), a Rab-like GTPase activator (VRP), and an ABA-responsive-element binding protein (FIP1). The alignment is based on the PSI-BLAST alignment of Doerks et al., (2000). Key structural residues in the MTMR2 PH-GRAM domain that are conserved among GRAM domain proteins are shaded gray. Gly-103 is shaded orange. Secondary structure elements in the PH-GRAM domain of MTMR2 are shown above the sequences. For clarity, the sequence of a long loop in FIP1 (p = PLSYKEGEQT) was omitted.
Molecular Cell  , DOI: ( /S (03) )

5. Figure 4 The MTMR2 Substrate Binding Pocket
(A) Structural alignment of MTMR2 (blue) and PTEN (yellow; PDB entry 1D5R). The P loops from both molecules are pink. The catalytic Asp on the WPD loop of PTEN, Asp-92, and Asn-355 from MTMR2 are shown as ball-and-sticks.
(B) Fo - Fc simulated annealed electron density omit map contoured at 3 σ. The map was calculated with phases from the final model except that the phosphate molecules and residues in the active site were omitted.
Molecular Cell  , DOI: ( /S (03) )

6. Figure 5 Model of Ins(1,3,5)P3 in the Active Site of MTMR2
(A) A schematic of the phosphate molecules and hydrogen bond network in the MTMR2 active site. Hydrogen bonds are shown as blue dotted lines.
(B) Model of Ins(1,3,5)P3 in the active site of MTMR2 with its D1 and D3 phosphate groups superimposed onto the phosphate molecules shown in (A).
(C) Phosphatase activity of MTMR2 mutants toward PI(3)P and PI(3,5)P2 substrates. Values are expressed as percent wild-type MTMR2 activity of three independent experiments (mean ± SEM).
Molecular Cell  , DOI: ( /S (03) )

7. Figure 6 Missense Disease Mutations
(A) Sequence conservation of MTM1 and MTMR2 and the location of missense disease mutations. The sequence of MTMR2 corresponding to the crystal structure was aligned with MTM1. Regions of identity are boxed and shaded. Arrows and ovals represent β strands and α helices, respectively. Missense disease mutations are marked with arrowheads.
(B) Van der Waals surface space-filled model of MTMR2. The view is the same as Figure 2A. The PH-GRAM domain is shown in green, the phosphatase domain in blue, and the active site motif (P loop) in yellow. Residues that are sites of missense disease mutations are red and labeled when >10% solvent accessible.
(C) View corresponding to a 180° rotation around a vertical axis with respect to Figure 6B. Solvent accessible residues are indicated.
Molecular Cell  , DOI: ( /S (03) )