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PDBsum entry 2gwo

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Hydrolase PDB id
2gwo
Jmol
Contents
Protein chain
169 a.a.
Waters ×260

References listed in PDB file
Key reference
Title Crystal structure of human tmdp, A testis-Specific dual specificity protein phosphatase: implications for substrate specificity.
Authors S.J.Kim, D.G.Jeong, T.S.Yoon, J.H.Son, S.K.Cho, S.E.Ryu, J.H.Kim.
Ref. Proteins, 2007, 66, 239-245. [DOI no: 10.1002/prot.21197]
PubMed id 17044055
Abstract
The testis- and skeletal-muscle-specific dual-specificity phosphatase (TMDP) is a member of the dual-specificity phosphatase (DSP) subgroup of protein tyrosine phosphatases. TMDP has similar activities toward both tyrosine and threonine phosphorylated substrates, and is supposed to be involved in spermatogenesis. Here, we report the crystal structure of human TMDP at a resolution of 2.4 A. In spite of high sequence similarity with other DSPs, the crystal structure of TMDP shows distinct structural motifs and surface properties. In TMDP, the alpha1-beta1 loop, a substrate recognition motif is located further away from the active site loop in comparison to prototype DSP Vaccinia H1 related phophatase (VHR), which preferentially dephosphorylates tyrosine phosphorylated substrates and down-regulates MAP kinase signaling. Residues in the active site residues of TMDP are smaller in size and more hydrophobic than those of VHR. In addition, TMDP cannot be aligned with VHR in loop beta3-alpha4. These differences in the active site of TMDP result in a flat and wide pocket structure, allowing equal binding of phosphotyrosine and phosphothreonine substrates.
Figure 1.
Figure 1. Overall structure of TMDP. (a) The TMDP structure is presented as a ribbon diagram. Secondary structural elements are labeled on the drawing. The active site cysteine is drawn as a ball-and-stick representation. Boundaries of the secondary structural elements are 1 (28-37), 1 (42-50), 2 (53-56), 2 (58-62), 3 (64-69), 3 (74-77), 4 (86-89), 4 (98-101), 5 (103-128), 5 (104-107), 6 (144-157), 7 (161-169), 8 (178-193). (b) The 2Fo-Fc electron density map around the active site is superimposed with the refined model. The map is contoured at the 1.1 level. (c) Structural comparison of TMDP (thick line) with VHR (thin line). C traces of two structures are superimposed using the O program.[18] The point of view is the same as in panel (a). The regions of TMDP that cannot be aligned are green whereas the corresponding regions of VHR are red. The position of C atom of Cys138 in TMDP is represented as a ball and labeled in the stereodiagram.
Figure 3.
Figure 3. A structural comparison of TMDP, VHR, and PTP1B. (a) TMDP is superposed with VHR complexed with its phospho-peptide (PDB code 1J4X). The worm model of TMDP is cyan whereas those of VHR and phospho-peptide are magenta and orange, respectively. The residues that contribute to the entrance to active sites are drawn by ball-and-stick model and labeled (TMDP: green, VHR: red, phosphorylated residues: grey). (b) The electrostatic potential surfaces of TMDP, VHR (PDB code: 1J4X) complexed with its phospho-peptide and PTP1B (PDB code: 2HNP) are compared. In a VHR complex, phospho-peptide is represented by stick model. Positive and negative potentials are blue and red, respectively. The dotted line indicates the borders that are rimmed by the surrounding loops to the active site. The surrounding loops and the active site cysteine residues are labeled in green and in black, respectively. The electrostatic surface potentials were calculated with contours from -10 (red) to + 10 (blue) kTe^-1 (k, Boltzmann's constant; T, temperature; e, electron) and with an exterior dielectric constant of 80. (c) The sliced views of active sites of TMDP, VHR (PDB code: 1VHR) and PTP1B (PDB code: 1AAX). The molecular surface diagrams are drawn as a basket-weaved model by using the VOIDOO program.[28] The molecular surfaces near the active sites reveal that the pocket depth of TMDP is shallow when compared with those of PTP1B and VHR. The surfaces of TMDP, VHR, and PTP1B are violet, navy, and orange, respectively.
The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2007, 66, 239-245) copyright 2007.
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