The Experts below are selected from a list of 92394 Experts worldwide ranked by ideXlab platform
Vicky Sophianopoulou - One of the best experts on this subject based on the ideXlab platform.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Abstract Amino Acid uptake in fungi is mediated by general and specialized members of the Yeast Amino Acid Transporter (YAT) family, a sub-branch of the Amino Acid Polyamine organoCation (APC) transporter superfamily. PrnB is a highly specific L-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced-fit docking, genetics and biochemical approaches to investigate the molecular basis of this difference and identified residues governing substrate binding and specificity. We demonstrate that L-proline is recognized by PrnB via interactions with residues within TMS1 (G56, T57), TMS3 (E138) and 6 (F248) while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), and TMS6 (F248), that are evolutionary conserved in YATs, while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F) and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently L-alanine, L-Azetidine-2-Carboxylic Acid and glycine without significantly affecting the apparent Km for L-proline. S253G and W351F could transport L-alanine, while T414S, despite displaying reduced proline uptake, could transport L-alanine and glycine, a phenotype suppressed by the S130C mutation. Combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport L-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core or affecting conformational changes of the transport cycle.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Amino Acid uptake in fungi is mediated by general and specialized members of the yeast amino Acid transporter (YAT) family, a branch of the amino Acid polyamine organocation (APC) transporter superfamily. PrnB, a highly specific l-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical approaches to investigate the molecular basis of this difference and identify residues governing substrate binding and specificity. We demonstrate that l-proline is recognized by PrnB via interactions with residues within TMS1 (Gly(56), Thr(57)), TMS3 (Glu(138)), and TMS6 (Phe(248)), which are evolutionary conserved in YATs, whereas specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently l-alanine, l-Azetidine-2-Carboxylic Acid, and glycine without significantly affecting the apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas T414S, despite displaying reduced proline uptake, could transport l-alanine and glycine, a phenotype suppressed by the S130C mutation. A combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport l-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core, or affecting conformational changes of the transport cycle.
Christos Gournas - One of the best experts on this subject based on the ideXlab platform.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Abstract Amino Acid uptake in fungi is mediated by general and specialized members of the Yeast Amino Acid Transporter (YAT) family, a sub-branch of the Amino Acid Polyamine organoCation (APC) transporter superfamily. PrnB is a highly specific L-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced-fit docking, genetics and biochemical approaches to investigate the molecular basis of this difference and identified residues governing substrate binding and specificity. We demonstrate that L-proline is recognized by PrnB via interactions with residues within TMS1 (G56, T57), TMS3 (E138) and 6 (F248) while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), and TMS6 (F248), that are evolutionary conserved in YATs, while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F) and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently L-alanine, L-Azetidine-2-Carboxylic Acid and glycine without significantly affecting the apparent Km for L-proline. S253G and W351F could transport L-alanine, while T414S, despite displaying reduced proline uptake, could transport L-alanine and glycine, a phenotype suppressed by the S130C mutation. Combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport L-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core or affecting conformational changes of the transport cycle.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Amino Acid uptake in fungi is mediated by general and specialized members of the yeast amino Acid transporter (YAT) family, a branch of the amino Acid polyamine organocation (APC) transporter superfamily. PrnB, a highly specific l-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical approaches to investigate the molecular basis of this difference and identify residues governing substrate binding and specificity. We demonstrate that l-proline is recognized by PrnB via interactions with residues within TMS1 (Gly(56), Thr(57)), TMS3 (Glu(138)), and TMS6 (Phe(248)), which are evolutionary conserved in YATs, whereas specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently l-alanine, l-Azetidine-2-Carboxylic Acid, and glycine without significantly affecting the apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas T414S, despite displaying reduced proline uptake, could transport l-alanine and glycine, a phenotype suppressed by the S130C mutation. A combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport l-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core, or affecting conformational changes of the transport cycle.
Emmanuel Mikros - One of the best experts on this subject based on the ideXlab platform.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Abstract Amino Acid uptake in fungi is mediated by general and specialized members of the Yeast Amino Acid Transporter (YAT) family, a sub-branch of the Amino Acid Polyamine organoCation (APC) transporter superfamily. PrnB is a highly specific L-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced-fit docking, genetics and biochemical approaches to investigate the molecular basis of this difference and identified residues governing substrate binding and specificity. We demonstrate that L-proline is recognized by PrnB via interactions with residues within TMS1 (G56, T57), TMS3 (E138) and 6 (F248) while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), and TMS6 (F248), that are evolutionary conserved in YATs, while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F) and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently L-alanine, L-Azetidine-2-Carboxylic Acid and glycine without significantly affecting the apparent Km for L-proline. S253G and W351F could transport L-alanine, while T414S, despite displaying reduced proline uptake, could transport L-alanine and glycine, a phenotype suppressed by the S130C mutation. Combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport L-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core or affecting conformational changes of the transport cycle.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Amino Acid uptake in fungi is mediated by general and specialized members of the yeast amino Acid transporter (YAT) family, a branch of the amino Acid polyamine organocation (APC) transporter superfamily. PrnB, a highly specific l-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical approaches to investigate the molecular basis of this difference and identify residues governing substrate binding and specificity. We demonstrate that l-proline is recognized by PrnB via interactions with residues within TMS1 (Gly(56), Thr(57)), TMS3 (Glu(138)), and TMS6 (Phe(248)), which are evolutionary conserved in YATs, whereas specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently l-alanine, l-Azetidine-2-Carboxylic Acid, and glycine without significantly affecting the apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas T414S, despite displaying reduced proline uptake, could transport l-alanine and glycine, a phenotype suppressed by the S130C mutation. A combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport l-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core, or affecting conformational changes of the transport cycle.
Alexandros Athanasopoulos - One of the best experts on this subject based on the ideXlab platform.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Abstract Amino Acid uptake in fungi is mediated by general and specialized members of the Yeast Amino Acid Transporter (YAT) family, a sub-branch of the Amino Acid Polyamine organoCation (APC) transporter superfamily. PrnB is a highly specific L-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced-fit docking, genetics and biochemical approaches to investigate the molecular basis of this difference and identified residues governing substrate binding and specificity. We demonstrate that L-proline is recognized by PrnB via interactions with residues within TMS1 (G56, T57), TMS3 (E138) and 6 (F248) while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), and TMS6 (F248), that are evolutionary conserved in YATs, while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F) and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently L-alanine, L-Azetidine-2-Carboxylic Acid and glycine without significantly affecting the apparent Km for L-proline. S253G and W351F could transport L-alanine, while T414S, despite displaying reduced proline uptake, could transport L-alanine and glycine, a phenotype suppressed by the S130C mutation. Combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport L-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core or affecting conformational changes of the transport cycle.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Amino Acid uptake in fungi is mediated by general and specialized members of the yeast amino Acid transporter (YAT) family, a branch of the amino Acid polyamine organocation (APC) transporter superfamily. PrnB, a highly specific l-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical approaches to investigate the molecular basis of this difference and identify residues governing substrate binding and specificity. We demonstrate that l-proline is recognized by PrnB via interactions with residues within TMS1 (Gly(56), Thr(57)), TMS3 (Glu(138)), and TMS6 (Phe(248)), which are evolutionary conserved in YATs, whereas specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently l-alanine, l-Azetidine-2-Carboxylic Acid, and glycine without significantly affecting the apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas T414S, despite displaying reduced proline uptake, could transport l-alanine and glycine, a phenotype suppressed by the S130C mutation. A combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport l-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core, or affecting conformational changes of the transport cycle.
Thomas Evangelidis - One of the best experts on this subject based on the ideXlab platform.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Abstract Amino Acid uptake in fungi is mediated by general and specialized members of the Yeast Amino Acid Transporter (YAT) family, a sub-branch of the Amino Acid Polyamine organoCation (APC) transporter superfamily. PrnB is a highly specific L-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced-fit docking, genetics and biochemical approaches to investigate the molecular basis of this difference and identified residues governing substrate binding and specificity. We demonstrate that L-proline is recognized by PrnB via interactions with residues within TMS1 (G56, T57), TMS3 (E138) and 6 (F248) while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), and TMS6 (F248), that are evolutionary conserved in YATs, while specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F) and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently L-alanine, L-Azetidine-2-Carboxylic Acid and glycine without significantly affecting the apparent Km for L-proline. S253G and W351F could transport L-alanine, while T414S, despite displaying reduced proline uptake, could transport L-alanine and glycine, a phenotype suppressed by the S130C mutation. Combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport L-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core or affecting conformational changes of the transport cycle.
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the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino Acid transporters
Journal of Biological Chemistry, 2015Co-Authors: Christos Gournas, Thomas Evangelidis, Alexandros Athanasopoulos, Emmanuel Mikros, Vicky SophianopoulouAbstract:Amino Acid uptake in fungi is mediated by general and specialized members of the yeast amino Acid transporter (YAT) family, a branch of the amino Acid polyamine organocation (APC) transporter superfamily. PrnB, a highly specific l-proline transporter, only weakly recognizes other Put4p substrates, its Saccharomyces cerevisiae orthologue. Taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical approaches to investigate the molecular basis of this difference and identify residues governing substrate binding and specificity. We demonstrate that l-proline is recognized by PrnB via interactions with residues within TMS1 (Gly(56), Thr(57)), TMS3 (Glu(138)), and TMS6 (Phe(248)), which are evolutionary conserved in YATs, whereas specificity is achieved by subtle amino Acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3 (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the specificity of PrnB, enabling it to recognize more efficiently l-alanine, l-Azetidine-2-Carboxylic Acid, and glycine without significantly affecting the apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas T414S, despite displaying reduced proline uptake, could transport l-alanine and glycine, a phenotype suppressed by the S130C mutation. A combination of all five Put4p-ressembling substitutions resulted in a functional allele that could also transport l-alanine and glycine, displaying a specificity profile impressively similar to that of Put4p. Our results support a model where residues in these positions determine specificity by interacting with the substrates, acting as gating elements, altering the flexibility of the substrate binding core, or affecting conformational changes of the transport cycle.
