PDBsum entry 4az1

Hydrolase

PDB id: 4az1

Contents

Protein chains

294 a.a.

Ligands

EDO

FMT ×5

Waters ×261

PDB id:

4az1

Name:

Hydrolase

Title:

Crystal structure of the trypanosoma cruzi protein tyrosine phosphatase tcptp1, a potential therapeutic target for chagas' disease

Structure:

Tyrosine specific protein phosphatase. Chain: a, b. Synonym: protein tyrosine phosphatase tcptp1. Engineered: yes

Source:

Trypanosoma cruzi. Organism_taxid: 5693. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.18Å R-factor: 0.191 R-free: 0.232

Authors:

G.T.Lountos,J.E.Tropea,D.S.Waugh

Key ref:

G.T.Lountos et al. (2013). Structure of the Trypanosoma cruzi protein tyrosine phosphatase TcPTP1, a potential therapeutic target for Chagas' disease. Mol Biochem Parasitol, 187, 1-8. PubMed id: 23137716

Date:

22-Jun-12 Release date: 21-Nov-12

Protein chains

Q4E4C8  (Q4E4C8_TRYCC) -  Tyrosine specific protein phosphatase, putative from Trypanosoma cruzi (strain CL Brener)

Seq: 325 a.a.

Struc: 294 a.a.

Mol Biochem Parasitol 187:1-8 (2013)

PubMed id: 23137716

Structure of the Trypanosoma cruzi protein tyrosine phosphatase TcPTP1, a potential therapeutic target for Chagas' disease.

G.T.Lountos, J.E.Tropea, D.S.Waugh.

ABSTRACT

Chagas' disease, a neglected tropical affliction transmitted by the flagellated protozoan Trypanosoma cruzi, is prevalent in Latin America and affects nearly 18 million people worldwide, yet few approved drugs are available to treat the disease. Moreover, the currently available drugs exhibit severe toxicity or are poorly effective in the chronic phase of the disease. This limitation, along with the large population at risk, underscores the urgent need to discover new molecular targets and novel therapeutic agents. Recently, the T. cruzi protein tyrosine phosphatase TcPTP1 has been implicated in the cellular differentiation and infectivity of the parasite and is therefore a promising target for the design of novel anti-parasitic drugs. Here, we report the X-ray crystal structure of TcPTP1 refined to a resolution of 2.18Å, which provides structural insights into the active site environment that can be used to initiate structure-based drug design efforts to develop specific TcPTP1 inhibitors. Potential strategies to develop such inhibitors are also discussed.