Comparative substrate recognition by bacterial and fungal purine transporters of the NAT/NCS2 family
| Autor: | Marina Koukaki, Panayiota Karatza, George Diallinas, Sophia Goudela, Stathis Frillingos |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Purine
Pyrimidine Stereochemistry Purine analogue medicine.disease_cause Xanthine Aspergillus nidulans Substrate Specificity Fungal Proteins chemistry.chemical_compound Structure-Activity Relationship Bacterial Proteins Xanthine/metabolism Candida albicans medicine Escherichia coli Nucleobase Transport Proteins Animals Fungal Proteins/chemistry/*metabolism Purine metabolism Molecular Biology Purines/metabolism biology Transporter Biological Transport Cell Biology biology.organism_classification Bacterial Proteins/chemistry/*metabolism Pyrimidines chemistry Biochemistry Purines Nucleobase Transport Proteins/chemistry/*metabolism Pyrimidines/metabolism |
| Zdroj: | Molecular membrane biology. 22(3) |
| ISSN: | 0968-7688 |
| Popis: | We compared the interactions of purines and purine analogues with representative fungal and bacterial members of the widespread Nucleobase-Ascorbate Transporter (NAT) family. These are: UapA, a well-studied xanthine-uric acid transporter of A. nidulans, Xut1, a novel transporter from C. albicans, described for the first time in this work, and YgfO, a recently characterized xanthine transporter from E. coli. Using transport inhibition experiments with 64 different purines and purine-related analogues, we describe a kinetic approach to build models on how NAT proteins interact with their substrates. UapA, Xut1 and YgfO appear to bind several substrates via interactions with both the pyrimidine and imidazol rings. Fungal homologues interact with the pyrimidine ring of xanthine and xanthine analogues via H-bonds, principally with N1-H and =O6, and to a lower extent with =O2. The E. coli homologue interacts principally with N3-H and =O2, and less strongly with N1-H and =O6. The basic interaction with the imidazol ring appears to be via a H-bond with N9. Interestingly, while all three homologues recognize xanthines with similar high affinities, interaction with uric acid or/and oxypurinol is transporter-specific. UapA recognizes uric acid with high affinity, principally via three H-bonds with =O2, =O6 and =O8. Xut1 has a 13-fold reduced affinity for uric acid, based on a different set of interactions involving =O8, and probably H atoms from positions N1, N3, N7 or N9. YgfO does not recognize uric acid at all. Both Xut1 and UapA recognize oxypurinol, but use different interactions reflected in a nearly 26-fold difference in their affinities for this drug, while YgfO interacts with this analogue very inefficiently. Mol Membr Biol |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |