PDBsum entry 3m4u

Hydrolase

PDB id: 3m4u

Contents

Protein chains

285 a.a. *

Ligands

PO4 ×2

Waters ×192

* Residue conservation analysis

PDB id:

3m4u

Name:

Hydrolase

Title:

Crystal structure of trypanosoma brucei protein tyrosine phosphatase tbptp1

Structure:

Tyrosine specific protein phosphatase, putative. Chain: a, b. Engineered: yes

Source:

Trypanosoma brucei. Organism_taxid: 5691. Gene: tb10.70.0070. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.39Å R-factor: 0.201 R-free: 0.256

Authors:

S.Chou,T.Alber,C.Grundner

Key ref:

S.Chou et al. (2010). The Trypanosoma brucei life cycle switch TbPTP1 is structurally conserved and dephosphorylates the nucleolar protein NOPP44/46. J Biol Chem, 285, 22075-22081. PubMed id: 20444707

Date:

12-Mar-10 Release date: 05-May-10

Protein chains

Q38AT7  (Q38AT7_TRYB2) -  Tyrosine specific protein phosphatase, putative from Trypanosoma brucei brucei (strain 927/4 GUTat10.1)

Seq: 306 a.a.

Struc: 285 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

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

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

Key reference

J Biol Chem 285:22075-22081 (2010)

PubMed id: 20444707

The Trypanosoma brucei life cycle switch TbPTP1 is structurally conserved and dephosphorylates the nucleolar protein NOPP44/46.

S.Chou, B.C.Jensen, M.Parsons, T.Alber, C.Grundner.

ABSTRACT

Trypanosoma brucei adapts to changing environments as it cycles through arrested and proliferating stages in the human and tsetse fly hosts. Changes in protein tyrosine phosphorylation of several proteins, including NOPP44/46, accompany T. brucei development. Moreover, inactivation of T. brucei protein tyrosine phosphatase 1 (TbPTP1) triggers differentiation of bloodstream stumpy forms into tsetse procyclic forms through unknown downstream effects. Here, we link these events by showing that NOPP44/46 is a major substrate of TbPTP1. TbPTP1 substrate-trapping mutants selectively enrich NOPP44/46 from procyclic stage cell lysates, and TbPTP1 efficiently and selectively dephosphorylates NOPP44/46 in vitro. To provide insights into the mechanism of NOPP44/46 recognition, we determined the crystal structure of TbPTP1. The TbPTP1 structure, the first of a kinetoplastid PTP, emphasizes the conservation of the protein tyrosine phosphatase (PTP) fold, extending to one of the most diverged eukaryotes. The structure reveals surfaces that may mediate substrate specificity and affords a template for the design of selective inhibitors to interfere with T. brucei transmission.