Substrate Selectivity of YgfU, a Uric Acid Transporter from Escherichia coli

Παπακώστας, Κωνσταντίνος; Frillingos, Stathis

doi:10.1074/jbc.m112.355818

Cited by 45 publications

(88 citation statements)

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“…As a result, homology modeling has been used as a reasonable alternative in cases where no x-ray structure is available (23,48,59,61,(67)(68)(69)(70)(71)(72)(73). Using this approach, combined with induced fit docking and a detailed characterization of the specificity profile, we identified 9 residues that are important for PrnB function, Gly 56 Table 5).…”

Section: Discussionmentioning

confidence: 99%

The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters

Gournas

Evangelidis

Αθανασόπουλος

et al. 2015

Journal of Biological Chemistry

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Background: PrnB, different from Put4p, its Saccharomyces cerevisiae orthologue, is a highly specific L-proline transporter of Aspergillus nidulans. Results: Identification of 12 residues important for PrnB activity and/or specificity. Put4p-mimicking mutants of PrnB recognize other Put4p substrates. Conclusion: Residues variable in the yeast amino acid transporter (YAT) family determine transporter specificity. Significance: Understanding the molecular mechanisms underlying amino acid recognition and translocation through YATs.

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Section: Discussionmentioning

confidence: 99%

The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters

Gournas

Evangelidis

Αθανασόπουλος

et al. 2015

Journal of Biological Chemistry

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“…Of the remaining members, YgfU is closely related in sequence and genomic locus with XanQ. YgfU is a proton-gradient dependent, low-affinity and high-capacity transporter for uric acid (Papakostas & Frillingos 2012).…”

Section: Bacterial Uric Acid Transportersmentioning

confidence: 99%

“…The entire picture of uric acid metabolism will advance our knowledge and give a wider selection of effective treatments for hyperuricemia. Papakostas and Frillingos (2012) …”

Section: Perspectivesmentioning

confidence: 99%

Uric acid transporters hiding in the intestine

Zhou

et al. 2016

Pharmaceutical Biology

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Context: Hyperuricaemia is known as an abnormally increased uric acid level in the blood. Although it was observed many years ago, since uric acid excretion via the intestine pathway accounted for approximately one-third of total elimination of uric acid, the molecular mechanism of 'extra-renal excretion' was poorly understood until the finding of uric acid transporters. Objective: The objective of this study was to gather all information related to uric acid transporters in the intestine and present this information as a comprehensive and systematic review article. Methods: A literature search was performed from various databases (e.g., Medline, Science Direct, Springer Link, etc.). The key terms included uric acid, transporter and intestine. The period for the search is from the 1950s to the present. The bibliographies of papers relating to the review subject were also searched for further relevant references. Results: The uric acid transporters identified in the intestine are discussed in this review. The solute carrier (SLC) transporters include GLUT9, MCT9, NPT4, NPT homolog (NPT5) and OAT10. The ATP binding cassette (ABC) transporters include ABCG2 (BCRP), MRP2 and MRP4. Bacterial transporter YgfU is a low-affinity and high-capacity transporter for uric acid. Conclusion: The present review may be helpful for further our understanding of hyperuricaemia and be of value in designing future studies on novel therapeutic pathways. ARTICLE HISTORY

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“…It is generally true that such important residues fall in one of the following three categories: (a) irreplaceable; (b) replaceable with few other side chains; (c) sensitive to inactivation of the Cys replacement by NEM. These three potential properties can be used to define the set of important residues of the study prototype, as deduced from Cys-scanning analysis data (Karena & Frillingos, 2011;Papakostas & Frillingos, 2012). It is also unequivocally true that this set of residues represents positions with a higher degree of side chain conservation than the rest of the protein and, in cases of transporters that have been studied thoroughly, correspond to a small percentage of the total amino acids in the sequence, usually 10-15% (Frillingos et al, 1998;Georgopoulou et al, 2010;Mermelekas et al, 2010;Tamura et al, 2003).…”

Section: Selecting New Homologs and Mutagenesis Targets To Studymentioning

confidence: 99%

“…In this respect, of particular interest are new homologs with distinct selectivity profiles relative to XanQ. One such homolog is UacT (more commonly known as YgfU), a low-affinity uric acid transporter from E. coli characterized recently (Papakostas & Frillingos, 2012). UacT is a proton-gradient-dependent, low-affinity (K m 0.5 mM) and high-capacity transporter for uric acid that also transports xanthine, but with disproportionately low capacity.…”

Section: Selection Of the Homolog To Study And The Mutagenesis Targetsmentioning

confidence: 99%