5B1S

Crystal structure of Trypanosoma cruzi spermidine synthase in complex with 2-(2-fluorophenyl)ethanamine

Summary for 5B1S

• Entry DOI: 10.2210/pdb5b1s/pdb
• Descriptor: Spermidine synthase, putative, 5'-[(S)-(3-AMINOPROPYL)(METHYL)-LAMBDA~4~-SULFANYL]-5'-DEOXYADENOSINE, 2-(2-fluorophenyl)ethanamine, ... (4 entities in total)
• Functional Keywords: polyamine synthesis, transferase
• Biological source: Trypanosoma cruzi strain CL Brener
• Total number of polymer chains: 4
• Total formula weight: 138397.35

Authors

Amano, Y.,Tateishi, Y. (deposition date: 2015-12-17, release date: 2016-12-21, Last modification date: 2023-11-08)

Primary citation

Yoshino, R.,Yasuo, N.,Hagiwara, Y.,Ishida, T.,Inaoka, D.K.,Amano, Y.,Tateishi, Y.,Ohno, K.,Namatame, I.,Niimi, T.,Orita, M.,Kita, K.,Akiyama, Y.,Sekijima, M.
In silico, in vitro, X-ray crystallography, and integrated strategies for discovering spermidine synthase inhibitors for Chagas disease
Sci Rep, 7:6666-6666, 2017

PubMed Abstract: Chagas disease results from infection by Trypanosoma cruzi and is a neglected tropical disease (NTD). Although some treatment drugs are available, their use is associated with severe problems, including adverse effects and limited effectiveness during the chronic disease phase. To develop a novel anti-Chagas drug, we virtually screened 4.8 million small molecules against spermidine synthase (SpdSyn) as the target protein using our super computer "TSUBAME2.5" and conducted in vitro enzyme assays to determine the half-maximal inhibitory concentration values. We identified four hit compounds that inhibit T. cruzi SpdSyn (TcSpdSyn) by in silico and in vitro screening. We also determined the TcSpdSyn-hit compound complex structure using X-ray crystallography, which shows that the hit compound binds to the putrescine-binding site and interacts with Asp171 through a salt bridge.

PubMed: 28751689
DOI: 10.1038/s41598-017-06411-9

Experimental method

X-RAY DIFFRACTION (1.58 Å)