PDBsum entry 3v4y

Hydrolase

PDB id: 3v4y

Contents

Protein chains

293 a.a.

41 a.a.

39 a.a.

39 a.a.

43 a.a.

Ligands

GOL ×10

15P

Metals

_MN ×8

Waters ×661

PDB id:

3v4y

Name:

Hydrolase

Title:

Crystal structure of the first nuclear pp1 holoenzyme

Structure:

Serine/threonine-protein phosphatase pp1-alpha catalytic subunit. Chain: a, c, e, g. Fragment: pp1 binding domain. Synonym: pp-1a. Engineered: yes. Nuclear inhibitor of protein phosphatase 1. Chain: b, d, f, h. Synonym: nipp-1, protein phosphatase 1 regulatory inhibitor subunit

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp1a, ppp1ca. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ppp1r8, ard1, nipp1. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.156 R-free: 0.196

Authors:

R.Page,W.Peti,N.E.O'Connell,S.Nichols

Key ref:

N.O'Connell et al. (2012). The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme. Structure, 20, 1746-1756. PubMed id: 22940584

Date:

15-Dec-11 Release date: 31-Oct-12

Protein chains

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

Seq: 330 a.a.

Struc: 293 a.a.

Protein chain

Q12972  (PP1R8_HUMAN) -  Nuclear inhibitor of protein phosphatase 1 from Homo sapiens

Seq: 351 a.a.

Struc: 41 a.a.

Protein chain

Q12972  (PP1R8_HUMAN) -  Nuclear inhibitor of protein phosphatase 1 from Homo sapiens

Seq: 351 a.a.

Struc: 39 a.a.*

Protein chain

Q12972  (PP1R8_HUMAN) -  Nuclear inhibitor of protein phosphatase 1 from Homo sapiens

Seq: 351 a.a.

Struc: 39 a.a.

Protein chain

Q12972  (PP1R8_HUMAN) -  Nuclear inhibitor of protein phosphatase 1 from Homo sapiens

Seq: 351 a.a.

Struc: 43 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, C, E, G: 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 2: Chains B, D, F, H: E.C.3.1.4.- - ?????

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

Added reference

Structure 20:1746-1756 (2012)

PubMed id: 22940584

The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme.

N.O'Connell, S.R.Nichols, E.Heroes, M.Beullens, M.Bollen, W.Peti, R.Page.

ABSTRACT

Regulation of protein phosphatase 1 (PP1) is controlled by a diverse array of regulatory proteins. However, how these proteins direct PP1 specificity is not well understood. More than one-third of the nuclear pool of PP1 forms a holoenzyme with the nuclear inhibitor of PP1, NIPP1, to regulate chromatin remodeling, among other essential biological functions. Here, we show that the PP1-binding domain of NIPP1 is an intrinsically disordered protein, which binds PP1 in an unexpected manner. NIPP1 forms an α helix that engages PP1 at a unique interaction site, using polar rather than hydrophobic contacts. Importantly, the structure also reveals a shared PP1 interaction site outside of the RVxF motif, the ΦΦ motif. Finally, we show that NIPP1:PP1 substrate selectivity is determined by altered electrostatics and enhanced substrate localization. Together, our results provide the molecular basis by which NIPP1 directs PP1 substrate specificity in the nucleus.