PDBsum entry 3egg

Hydrolase

PDB id: 3egg

Contents

Protein chains

294 a.a. *

160 a.a. *

66 a.a. *

Ligands

GOL ×7

MES ×3

Metals

_MN ×4

Waters ×521

* Residue conservation analysis

PDB id:

3egg

Name:

Hydrolase

Title:

Crystal structure of a complex between protein phosphatase 1 alpha (pp1) and the pp1 binding and pdz domains of spinophilin

Structure:

Serine/threonine-protein phosphatase pp1-alpha catalytic subunit. Chain: a, b. Synonym: pp-1a. Engineered: yes. Spinophilin. Chain: c, d. Fragment: pp1 binding and pdz domains. Synonym: neurabin-ii, neurabin-2, protein phosphatase 1 regulatory

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp1ca, ppp1a. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Rat. Organism_taxid: 10116.

Resolution:

1.85Å R-factor: 0.181 R-free: 0.211

Authors:

M.J.Ragusa,R.Page,W.Peti

Key ref:

M.J.Ragusa et al. (2010). Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites. Nat Struct Biol, 17, 459-464. PubMed id: 20305656

Date:

10-Sep-08 Release date: 23-Mar-10

Protein chains

P62136  (PP1A_HUMAN) -  Serine/threonine-protein phosphatase PP1-alpha catalytic subunit from Homo sapiens

Seq: 330 a.a.

Struc: 294 a.a.

Protein chain

O35274  (NEB2_RAT) -  Neurabin-2 from Rattus norvegicus

Seq: 817 a.a.

Struc: 160 a.a.

Protein chain

O35274  (NEB2_RAT) -  Neurabin-2 from Rattus norvegicus

Seq: 817 a.a.

Struc: 66 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: 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

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

Added reference

Nat Struct Biol 17:459-464 (2010)

PubMed id: 20305656

Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites.

M.J.Ragusa, B.Dancheck, D.A.Critton, A.C.Nairn, R.Page, W.Peti.

ABSTRACT

The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets. PP1 associates with >or=200 regulatory proteins to form highly specific holoenzymes. These regulatory proteins target PP1 to its point of action within the cell and prime its enzymatic specificity for particular substrates. However, how they direct PP1's specificity is not understood. Here we show that spinophilin, a neuronal PP1 regulator, is entirely unstructured in its unbound form, and it binds PP1 through a folding-upon-binding mechanism in an elongated fashion, blocking one of PP1's three putative substrate binding sites without altering its active site. This mode of binding is sufficient for spinophilin to restrict PP1's activity toward a model substrate in vitro without affecting its ability to dephosphorylate its neuronal substrate, glutamate receptor 1 (GluR1). Thus, our work provides the molecular basis for the ability of spinophilin to dictate PP1 substrate specificity.