PDBsum entry: 1wao

Hydrolase

PDB id: 1wao

Contents

Protein chains

471 a.a. *

Metals

_MN ×8

* Residue conservation analysis

PDB id:

1wao

Name:

Hydrolase

Title:

Pp5 structure

Structure:

Serine/threonine protein phosphatase 5. Chain: 1, 2, 3, 4. Synonym: pp5, protein phosphatase t, pp-t, ppt, protein phosphatase 5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.90Å R-factor: 0.247 R-free: 0.290

Authors:

D.Barford

Key ref:

J.Yang et al. (2005). Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. EMBO J, 24, 1. PubMed id: 15577939 DOI: 10.1038/sj.emboj.7600496

Date:

27-Oct-04 Release date: 22-Feb-05

Protein chains

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

Seq: 499 a.a.

Struc: 471 a.a.

Enzyme reactions

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

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cell soma (6 terms)
• Biological process: signal transduction (7 terms)
• Biochemical function: binding (7 terms)

Added reference

DOI no: 10.1038/sj.emboj.7600496

EMBO J 24:1 (2005)

PubMed id: 15577939

Molecular basis for TPR domain-mediated regulation of protein phosphatase 5.

J.Yang, S.M.Roe, M.J.Cliff, M.A.Williams, J.E.Ladbury, P.T.Cohen, D.Barford.

ABSTRACT

Protein phosphatase 5 (Ppp5) is a serine/threonine protein phosphatase comprising a regulatory tetratricopeptide repeat (TPR) domain N-terminal to its phosphatase domain. Ppp5 functions in signalling pathways that control cellular responses to stress, glucocorticoids and DNA damage. Its phosphatase activity is suppressed by an autoinhibited conformation maintained by the TPR domain and a C-terminal subdomain. By interacting with the TPR domain, heat shock protein 90 (Hsp90) and fatty acids including arachidonic acid stimulate phosphatase activity. Here, we describe the structure of the autoinhibited state of Ppp5, revealing mechanisms of TPR-mediated phosphatase inhibition and Hsp90- and arachidonic acid-induced stimulation of phosphatase activity. The TPR domain engages with the catalytic channel of the phosphatase domain, restricting access to the catalytic site. This autoinhibited conformation of Ppp5 is stabilised by the C-terminal alphaJ helix that contacts a region of the Hsp90-binding groove on the TPR domain. Hsp90 activates Ppp5 by disrupting TPR-phosphatase domain interactions, permitting substrate access to the constitutively active phosphatase domain, whereas arachidonic acid prompts an alternate conformation of the TPR domain, destabilising the TPR-phosphatase domain interface.

Selected figure(s)

Figure 1.
Figure 1 Structure of human Ppp5. Ribbon representation of Ppp5 with the TPR and phosphatase domains coloured blue and pink, respectively. The C-terminal subdomain including the J helix is in yellow. Metal ions of the binuclear centre are shown as blue spheres. The figures were produced using PYMOL (http://www.pymol.org).

Figure 3.
Figure 3 Phosphatase -TPR domain interactions. (A) The phosphatase domain and C-terminal subdomain are represented with a molecular surface, and the TPR domain as ribbon. Intra-TPR turns form a ridge that inserts into the phosphatase domain catalytic channel, with Glu76 of TPR-2 projecting towards the binuclear metal centre. (B) Glu76 of the TPR-2 interacts with Arg275 and Tyr451 at the catalytic site. Metal ions are indicated as M1 and M2 and side chains of metal ion-binding residues are coloured pink. (C) The J helix forms hydrophobic contacts with the TPR domain. Detailed interactions involving Leu493 and Leu494 of the J helix with TPR-3 and 7 of the TPR domain are shown. The amide side chain of Gln495 donates hydrogen bonds to the main-chain carbonyls of 489 and 490, stabilising the position of the J helix.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2005, 24, 1-0) copyright 2005.

Figures were selected by an automated process.