Document Detail


Structural model of a putrescine-cadaverine permease from Trypanosoma cruzi predicts residues vital for transport and ligand binding.
MedLine Citation:
PMID:  23535070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The TcPOT1.1 gene from Trypanosoma cruzi encodes a high affinity putrescine-cadaverine transporter belonging to the APC (amino acid/polyamine/organocation) transporter superfamily. No experimental three-dimensional structure exists for any eukaryotic member of the APC family, and thus the structural determinants critical for function of these permeases are unknown. To elucidate the key residues involved in putrescine translocation and recognition by this APC family member, a homology model of TcPOT1.1 was constructed on the basis of the atomic co-ordinates of the Escherichia coli AdiC arginine/agmatine antiporter crystal structure. The TcPOT1.1 homology model consisted of 12 transmembrane helices with the first ten helices organized in two V-shaped antiparallel domains with discontinuities in the helical structures of transmembrane spans 1 and 6. The model suggests that Trp241 and a Glu247-Arg403 salt bridge participate in a gating system and that Asn245, Tyr148 and Tyr400 contribute to the putrescine-binding pocket. To test the validity of the model, 26 site-directed mutants were created and tested for their ability to transport putrescine and to localize to the parasite cell surface. These results support the robustness of the TcPOT1.1 homology model and reveal the importance of specific aromatic residues in the TcPOT1.1 putrescine-binding pocket.
Authors:
Radika Soysa; Hanka Venselaar; Jacqueline Poston; Buddy Ullman; Marie-Pierre Hasne
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  452     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-03     Completed Date:  2013-08-06     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  423-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport Systems / chemistry*,  metabolism
Cadaverine / chemistry*,  metabolism
Cells, Cultured
Ligands
Membrane Transport Proteins / chemistry*,  metabolism
Models, Molecular*
Predictive Value of Tests
Protein Binding / physiology
Protein Transport / physiology
Putrescine / chemistry*,  metabolism
Trypanosoma cruzi / enzymology*
Grant Support
ID/Acronym/Agency:
AI041622/AI/NIAID NIH HHS; R01 AI041622/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/Ligands; 0/Membrane Transport Proteins; L90BEN6OLL/Cadaverine; V10TVZ52E4/Putrescine
Comments/Corrections

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