PDBsum entry: 1s95

Hydrolase

PDB id: 1s95

Contents

Protein chains

324 a.a. *

Ligands

PO4 ×2

MPD ×2

Metals

_MN ×4

Waters ×463

* Residue conservation analysis

PDB id:

1s95

Name:

Hydrolase

Title:

Structure of serine/threonine protein phosphatase 5

Structure:

Serine/threonine protein phosphatase 5. Chain: a, b. Fragment: catalytic domain. Synonym: pp5, protein phosphatase t, pp-t, ppt. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp5c, ppp5. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.171 R-free: 0.209

Authors:

M.R.Swingle,R.E.Honkanen,E.M.Ciszak

Key ref:

M.R.Swingle et al. (2004). Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5. J Biol Chem, 279, 33992-33999. PubMed id: 15155720 DOI: 10.1074/jbc.M402855200

Date:

03-Feb-04 Release date: 24-Aug-04

Protein chains

P53041  (PPP5_HUMAN) -  Serine/threonine-protein phosphatase 5

Seq: 499 a.a.

Struc: 324 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.16 - Phosphoprotein phosphatase.
• Reaction: A phosphoprotein + H₂O = a protein + phosphate

phosphoprotein + H(2)O = protein + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (2 terms)
• Biological process: protein dephosphorylation (1 term)
• Biochemical function: hydrolase activity (4 terms)

Added reference

DOI no: 10.1074/jbc.M402855200

J Biol Chem 279:33992-33999 (2004)

PubMed id: 15155720

Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5.

M.R.Swingle, R.E.Honkanen, E.M.Ciszak.

ABSTRACT

Serine/threonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell growth and cellular responses to stress. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp271-M1:M2-W1-His427-His304-Asp274 catalytic motif (where M1 and M2 are metals and W1 is a water molecule). The structure of PP5c provides a structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Selected figure(s)

Figure 2.
FIG. 2. Catalytic site of PP5c. A, a stereoview of a 2F[o] - F[c] electron density map contoured at a 1.2 level overlaying the positions of amino acids and phosphate ion shown as stick models, and water molecules and metal ions shown as spheres. B, detailed representation of contacts within the active site. The hydrogen bonds are shown as yellow dotted lines, and coordination bonds to metal ions are shown as red solid lines. The green dotted line between the hydroxyl (W1) ion and phosphorus atom (P) represents a close contact (2.9 Å) suggestive of a near attack configuration in metal ion-mediated hydrolysis of phosphoprotein substrates.

Figure 3.
FIG. 3. Schematic representation of metal ion-mediated hydrolysis of substrate derived from the crystal structure of PP5c. The attacking hydroxide W1 is shown in blue, and the leaving group of the substrate is in green. The substrate, the planar PO[3] moiety of the transition state, and the phosphate product are all shown in red. Solid lines to the metal ions denote metal-ligand bonds, and solid or dashed wedges indicate metal-ligand bonds directed above or below the plane of the page, respectively. Wavy lines to the metal ions indicate strained contacts with poor coordination geometry. Dotted lines indicate hydrogen bonds, and the nearly dissociated axial bonds in the transition state are shown by half-dotted double lines.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 33992-33999) copyright 2004.

Figures were selected by an automated process.