PDBsum entry 1d5r

Hydrolase

PDB id: 1d5r

Contents

Protein chain

307 a.a. *

Ligands

TLA

Waters ×382

* Residue conservation analysis

PDB id:

1d5r

Name:

Hydrolase

Title:

Crystal structure of the pten tumor suppressor

Structure:

Phosphoinositide phosphatase pten. Chain: a. Fragment: residues 7-353. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.

Resolution:

2.10Å R-factor: 0.224 R-free: 0.276

Authors:

J.O.Lee,H.Yang,M.-M.Georgescu,A.Di Cristofano,N.P.Pavletich

Key ref:

J.O.Lee et al. (1999). Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell, 99, 323-334. PubMed id: 10555148 DOI: 10.1016/S0092-8674(00)81663-3

Date:

11-Oct-99 Release date: 04-Nov-99

Protein chain

P60484  (PTEN_HUMAN) -  Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN from Homo sapiens

Seq: 403 a.a.

Struc: 307 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.1.3.- - ?????
• Enzyme class 2: E.C.3.1.3.16 - protein-serine/threonine phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
  2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
• Enzyme class 3: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
• Enzyme class 4: E.C.3.1.3.67 - phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase.

Pathway:

• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + phosphate
• Cofactor: Mg(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0092-8674(00)81663-3

Cell 99:323-334 (1999)

PubMed id: 10555148

Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.

J.O.Lee, H.Yang, M.M.Georgescu, A.Di Cristofano, T.Maehama, Y.Shi, J.E.Dixon, P.Pandolfi, N.P.Pavletich.

ABSTRACT

The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. The structure also reveals that PTEN has a C2 domain. The PTEN C2 domain binds phospholipid membranes in vitro, and mutation of basic residues that could mediate this reduces PTEN's membrane affinity and its ability to suppress the growth of glioblastoma tumor cells. The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane.

Selected figure(s)

Figure 2.
Figure 2. The PTEN Phosphatase Domain Has the Same Fold as the Dual Specificity Phosphatase VHR, but the Structure Differs around the Active Site(A) Superimposition of the PTEN phosphatase domain and VHR structures. The structural elements around the active site that differ in the two structures—the pβ2-α1, “TI”, and “WPD” loops—are in blue for PTEN and green for VHR.(B) Slice of the active site molecular surface, represented as a wire mesh, shows the larger size of the PTEN active site pocket compared to VHR and PTP1B. View is rotated approximately 180° about the vertical axis of Figure 2A.(C) Comparison of the active site structural elements and active site residues of PTEN, VHR, and PTP1B. Blue, green, and magenta spheres near the catalytic Cys-124 indicate the positions of a carboxylate carbon of tartrate in PTEN, the sulfur atom of sulfate in VHR, and the phosphorous atom of phosphotyrosine in PTP1B, respectively. PTEN residues are labeled, and residues of VHR and PTP1B are labeled only when they differ from PTEN. Orientation as in Figure 2B.(D) Close-up view of the PTEN active site, showing the contacts made with the tartrate molecule (green dotted lines). Fo-Fc difference electron density around the tartrate molecule is shown in magenta. The map was calculated at 2.1 Å using a PTEN model before any tartrate atoms were built; it was contoured at 2.5 σ.

Figure 6.
Figure 6. The PTEN Phosphatase and C2 Domains Pack across an Extensive Interface that Is Targeted by Tumorigenic Mutations(A) The interface consists of the “WPD” loop, “TI” loop, and pα6 helix from the phosphatase domain (blue), and cβ5, cβ6, cα1, and cα2 from the C2 domain (magenta). The hydrogen bond networks in the interface are shown as green dotted lines.(B) Superposition of PTEN (red) and PLCδ1 (green). Their C2 domains are shown as backbone traces, and their respective catalytic domains as dot surfaces. The active sites in both cases are located on the same face with the CBR3 loops.

The above figures are reprinted by permission from Cell Press: Cell (1999, 99, 323-334) copyright 1999.

Figures were selected by an automated process.