4AZ1

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

Summary for 4AZ1

• Entry DOI: 10.2210/pdb4az1/pdb
• Descriptor: TYROSINE SPECIFIC PROTEIN PHOSPHATASE, 1,2-ETHANEDIOL, FORMIC ACID, ... (4 entities in total)
• Functional Keywords: hydrolase, drug design
• Biological source: TRYPANOSOMA CRUZI
• Total number of polymer chains: 2
• Total formula weight: 67963.60

Authors

Lountos, G.T.,Tropea, J.E.,Waugh, D.S. (deposition date: 2012-06-22, release date: 2012-11-21, Last modification date: 2023-12-20)

Primary citation

Lountos, G.T.,Tropea, J.E.,Waugh, D.S.
Structure of the Trypanosoma Cruzi Protein Tyrosine Phosphatase Tcptp1, a Potential Therapeutic Target for Chagas' Disease.
Mol.Biochem.Parasitol., 187:1-, 2012

PubMed 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 2.18 Å, 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.

PubMed: 23137716
DOI: 10.1016/J.MOLBIOPARA.2012.10.006

Experimental method

X-RAY DIFFRACTION (2.181 Å)