PDBsum entry 4xpn

Hydrolase

PDB id: 4xpn

Contents

Protein chains

296 a.a.

16 a.a.

14 a.a.

Ligands

PO4 ×2

GOL ×2

Metals

_MN ×4

Waters ×223

PDB id:

4xpn

Name:

Hydrolase

Title:

Crystal structure of protein phosphate 1 complexed with pp1 binding domain of gadd34

Structure:

Serine/threonine-protein phosphatase pp1-alpha catalytic subunit. Chain: a, c. Fragment: unp residues 7-300. Synonym: pp-1a. Engineered: yes. Protein phosphatase 1 regulatory subunit 15a. Chain: b, d. Fragment: unp residues 552-591.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp1ca, ppp1a. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ppp1r15a, gadd34. Expression_system_taxid: 562

Resolution:

2.29Å R-factor: 0.161 R-free: 0.205

Authors:

M.S.Choy,W.Peti,R.Page

Key ref:

M.S.Choy et al. (2015). Structural and Functional Analysis of the GADD34:PP1 eIF2α Phosphatase. Cell Rep, 11, 1885-1891. PubMed id: 26095357 DOI: 10.1016/j.celrep.2015.05.043

Date:

17-Jan-15 Release date: 01-Jul-15

Protein chains

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

Seq: 330 a.a.

Struc: 296 a.a.*

Protein chain

O75807  (PR15A_HUMAN) -  Protein phosphatase 1 regulatory subunit 15A from Homo sapiens

Seq: 674 a.a.

Struc: 16 a.a.

Protein chain

O75807  (PR15A_HUMAN) -  Protein phosphatase 1 regulatory subunit 15A from Homo sapiens

Seq: 674 a.a.

Struc: 14 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, C: 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

O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

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

Added reference

DOI no: 10.1016/j.celrep.2015.05.043

Cell Rep 11:1885-1891 (2015)

PubMed id: 26095357

Structural and Functional Analysis of the GADD34:PP1 eIF2α Phosphatase.

M.S.Choy, P.Yusoff, I.C.Lee, J.C.Newton, C.W.Goh, R.Page, S.Shenolikar, W.Peti.

ABSTRACT

The attenuation of protein synthesis via the phosphorylation of eIF2α is a major stress response of all eukaryotic cells. The growth-arrest- and DNA-damage-induced transcript 34 (GADD34) bound to the serine/threonine protein phosphatase 1 (PP1) is the necessary eIF2α phosphatase complex that returns mammalian cells to normal protein synthesis following stress. The molecular basis by which GADD34 recruits PP1 and its substrate eIF2α are not fully understood, hindering our understanding of the remarkable selectivity of the GADD34:PP1 phosphatase for eIF2α. Here, we report detailed structural and functional analyses of the GADD34:PP1 holoenzyme and its recruitment of eIF2α. The data highlight independent interactions of PP1 and eIF2α with GADD34, demonstrating that GADD34 functions as a scaffold both in vitro and in cells. This work greatly enhances our molecular understanding of a major cellular eIF2α phosphatase and establishes the foundation for future translational work.