PDBsum entry 1s70

Hydrolase

PDB id: 1s70

Contents

Protein chains

309 a.a. *

291 a.a. *

Ligands

PGE

Metals

_MN ×2

Waters ×227

* Residue conservation analysis

PDB id:

1s70

Name:

Hydrolase

Title:

Complex between protein ser/thr phosphatase-1 (delta) and the myosin phosphatase targeting subunit 1 (mypt1)

Structure:

Serine/threonine protein phosphatase pp1-beta (or delta) catalytic subunit. Chain: a. Synonym: pp-1b. Engineered: yes. Mutation: yes. 130 kda myosin-binding subunit of smooth muscle myosin phophatase (m130). Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp1cb. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031.

Biol. unit:

Dimer (from PQS)

Resolution:

2.70Å R-factor: 0.223 R-free: 0.293

Authors:

F.Kerff,M.Terrak,R.Dominguez

Key ref:

M.Terrak et al. (2004). Structural basis of protein phosphatase 1 regulation. Nature, 429, 780-784. PubMed id: 15164081 DOI: 10.1038/nature02582

Date:

28-Jan-04 Release date: 22-Jun-04

Protein chain

P62207  (PP1B_CHICK) -  Serine/threonine-protein phosphatase PP1-beta catalytic subunit from Gallus gallus

Seq: 327 a.a.

Struc: 309 a.a.

Protein chain

Q90623  (MYPT1_CHICK) -  Protein phosphatase 1 regulatory subunit 12A from Gallus gallus

Seq: 1004 a.a.

Struc: 291 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: 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 A, B: E.C.3.1.3.53 - [myosin-light-chain] phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[myosin light chain] + H2O = L-seryl-[myosin light chain] + phosphate
  2. O-phospho-L-threonyl-[myosin light chain] + H2O = L-threonyl-[myosin light chain] + phosphate

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

reference

DOI no: 10.1038/nature02582

Nature 429:780-784 (2004)

PubMed id: 15164081

Structural basis of protein phosphatase 1 regulation.

M.Terrak, F.Kerff, K.Langsetmo, T.Tao, R.Dominguez.

ABSTRACT

The coordinated and reciprocal action of serine/threonine (Ser/Thr) protein kinases and phosphatases produces transient phosphorylation, a fundamental regulatory mechanism for many biological processes. The human genome encodes a far greater number of Ser/Thr protein kinases than of phosphatases. Protein phosphatase 1 (PP1), in particular, is ubiquitously distributed and regulates a broad range of cellular functions, including glycogen metabolism, cell-cycle progression and muscle relaxation. PP1 has evolved effective catalytic machinery but lacks substrate specificity. Substrate specificity is conferred upon PP1 through interactions with a large number of regulatory subunits. The regulatory subunits are generally unrelated, but most possess the RVxF motif, a canonical PP1-binding sequence. Here we reveal the crystal structure at 2.7 A resolution of the complex between PP1 and a 34-kDa N-terminal domain of the myosin phosphatase targeting subunit MYPT1. MYPT1 is the protein that regulates PP1 function in smooth muscle relaxation. Structural elements amino- and carboxy-terminal to the RVxF motif of MYPT1 are positioned in a way that leads to a pronounced reshaping of the catalytic cleft of PP1, contributing to the increased myosin specificity of this complex. The structure has general implications for the control of PP1 activity by other regulatory subunits.

Selected figure(s)

Figure 1.
Figure 1: General fold of the PP1 delta--MYPT1[1 -299] complex. a, Ribbon representation: PP1 ; -helices and loops (blue) and -strands (magenta); and MYPT1 (red). The two cations in the catalytic site are coloured orange. The ankyrin repeats of MYPT1 are numbered 1 to 8 from the N to the C terminus. The major contacts with PP1 involve three separate regions of MYPT1: the N-terminal arm, the RVxF motif and the second group of ankyrin repeats, which interact mainly with PP1 residues Tyr A305 and Tyr A307. b, Two surface representations of the complex, rotated by 90 degrees (PP1 , blue; MYPT1, red).

Figure 2.
Figure 2: Electrostatic surface representations of the PP1 delta--MYPT1[1 -299] complex. a -c, Surfaces of PP1 (a), MYPT1 (b) and their complex (c) calculated using identical parameters (red and blue indicate regions charged negatively and positively, respectively). The Y-shaped catalytic cleft of PP1 is composed of three grooves: hydrophobic, acidic and C-terminal. The 12 - 13 loop separates the acidic and the C-terminal grooves. The reshaping of the catalytic cleft of PP1 results from the binding of the N terminus of MYPT1 near the hydrophobic groove and the addition of the acidic cleft of the ankyrin repeats at the other end of the cleft. d, Sequences of the RLC around Ser 19 and the MYPT1 around the regulatory phosphorylation sites Thr 695 and Thr 850. Note the existing charge complementarity between these sequences and the catalytic cleft of myosin phosphatase.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 429, 780-784) copyright 2004.

Figures were selected by the author.