Crystal Structure of ADP-ribosylated Ribosomal Translocase from Saccharomyces cerevisiae

The crystal structure of ADP-ribosylated yeast elongation factor 2 in the presence of sordarin and GDP has been determined at 2.6 Å resolution. The diphthamide at the tip of domain IV, which is the target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A, contains a covalently attached ADP-ribose that functions as a very potent inhibitor of the factor. We have obtained an electron density map of ADP-ribosylated translation factor 2 revealing both the ADP-ribosylation and the diphthamide. This is the first structure showing the conformation of an ADP-ribosylated residue and confirms the inversion of configuration at the glycosidic linkage. Binding experiments show that the ADP-ribosylation has and exotoxin the and that of the translation factor the in the of the The crystal structure of ADP-ribosylated yeast elongation factor 2 in the presence of sordarin and GDP has been determined at 2.6 Å resolution. The diphthamide at the tip of domain IV, which is the target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A, contains a covalently attached ADP-ribose that functions as a very potent inhibitor of the factor. We have obtained an electron density map of ADP-ribosylated translation factor 2 revealing both the ADP-ribosylation and the diphthamide. This is the first structure showing the conformation of an ADP-ribosylated residue and confirms the inversion of configuration at the glycosidic linkage. Binding experiments show that the ADP-ribosylation has and exotoxin the and that of the translation factor the in the of the elongation factor 2 elongation factor exotoxin ADP-ribosylated elongation factor elongation aeruginosa exotoxin a electron elongation factor exotoxin ADP-ribosylated elongation factor elongation aeruginosa exotoxin a electron the in the elongation of in the is the the and the is the the the for the crystal structure of yeast in the presence and of the sordarin This structure of the inhibitor the of the This is of both and the the showing that the IV, and and have that in and that both a and of domain in a in that and as domain for and This is in the in of the in contains a which a as diphthamide This residue is at in domain of yeast of in the have that the residue is the and This has the that the tip of domain the diphthamide have a in the the is in and is and of diphthamide at experiments the diphthamide have that the diphthamide residue is for diphthamide of is the for diphtheria toxin and Pseudomonas aeruginosa exotoxin which both the of ADP-ribose at the diphthamide in of the in a and and of the and and that the a an This is the inversion of configuration for the glycosidic the and diphthamide The inversion is the of the a the in diphthamide have that in the of diphthamide both diphtheria toxin and and has as an residue the crystal structure of that is a the of domain that is the of that is the ADP-ribosylation of and of the of the structure of domain of exotoxin in the that and of the a in and a of and diphtheria has been The the ADP-ribose of the diphthamide residue of and This that the diphthamide residue is a of and is a target for has been that the the toxin in that a of the the and that the of the in the of in toxin and the of the ADP-ribosylation of is and for the in have the structure of ADP-ribosylated diphthamide in yeast and in GDP and the inhibitor The crystal structure the inversion of configuration of the of the of and of the diphthamide residue the structure that the in and the in is the in the that the of the diphthamide is the at the The structure of the the electron density for the diphthamide structure of contains electron density for GDP and which in a of the in the the of GDP We showing that has the domain of as is that both and and GDP and in show that yeast a yeast and the for sordarin The structure of the ADP-ribosylated diphthamide is the first structure showing the conformation of an ADP-ribose covalently attached a target residue and the of ADP-ribosylation and the the elongation of the that is of the the a of of as The of a and as of of of in and The a at for the and a in The a The a in and a and of and a residue the and both and as Binding as The for determined the as of the of is the in for is the in at of the is the for the of and is the of of Binding of and sordarin in the of of the as a of a of in the presence of at in an of of at and the at in a The and for for the and the the The for the factor the factor for sordarin determined the as for the sordarin the Binding the of a of in of The for and a of a in and at for The in and of in sordarin as the very in a a for of both and at The and and and in of the ADP-ribosylated diphthamide the which and and for The ADP-ribosylated diphthamide of in and the density The structure and and the in The and structure for the structure of ADP-ribosylated at the the at the at in in for for the of a of and the and structure factor and is a factor. is a of in The as for the determined structure at Å and at the at in in for for the of a and the and structure factor and is a is a of in The as for the determined structure at Å in a of and the the and in the of This that the of the the of of the for the The of for a This the the in and the the the determined and for the and presence of the the the toxin for that the of the The a The of the for in a the and of for the the ADP-ribosylated of and a the the and the and a of the The of and that at a have determined the for and GDP yeast of GDP in the of the of the of the at of of the and the of for and GDP show that ADP-ribosylation of has very for the and that in for and The of in for and for the and which the experiments as yeast ADP-ribose for determined experiments as yeast ADP-ribose for determined in a structure of in the inhibitor and as for the structure sordarin in a IV, and The for sordarin yeast in the of determined in of the of the at of and is for sordarin which the that the sordarin the of a of 2.6 Å in and sordarin The the of in sordarin and GDP the of the the structure the crystal and the the structure an map that electron density for the ADP-ribose and and and of the a of Å The ADP-ribosylation at the is in the electron density map the and the for a the density the the density for the first and in and the map density for the which has of the ADP-ribose electron density and the in electron density map density for the diphthamide attached the at the of the electron density for the is density for the and in the density of and the diphthamide and in an of and an of density for the in the electron density map that the The the attached the of the electron density map an inversion of configuration of the the and the the in The ADP-ribosylated diphthamide is at the tip of domain the ADP-ribose a of the crystal a the of the The and a of the of the attached the of the diphthamide. the which the in that The of the ADP-ribose have the of ADP-ribosylated of the 2.6 Å electron density map residue of the the diphthamide and ADP-ribose The map at of a electron density map the ADP-ribosylated diphthamide residue the of the diphthamide and at of the electron density map the ADP-ribosylated diphthamide the of at The a residue a ADP-ribose and The diphthamide is at the tip of domain the the diphthamide is in a the ADP-ribose and and of a in the crystal Å the The of the diphthamide is Å at the of the the diphthamide is Å at of GDP Binding electron density map the of GDP and very density for GDP for the GDP is in a the and and in and in and in the and in the the and and density at the is as an and is and the of the an as in the density for is the of GDP and structure contains a of in the for the in the has is in the and of GDP and GDP of the electron density map GDP and a of the structure GDP and and at GDP and in the the and The map is a GDP and a and and at the and the at in the the Å of the and and the GDP structure ADP-ribosylation of a of both and a very in and of the the and of and and Pseudomonas in which an as a a for of both the and of target have been has determined the structure of the of the as the for structure is the first of ADP-ribosylated and that the is attached the diphthamide of is and the the sordarin of of is and of of the at the of domain is and in both of that the presence of sordarin the and the of the in show that the conformation of IV, and is the ADP-ribosylation the of the the ADP-ribosylated is of of translation ADP-ribosylation of is experiments have that and ADP-ribosylation This that in the of the of the This and which has been for a very in have a in the of the as as a in and of ADP-ribosylation a the of that ADP-ribosylation of the of in the of a of of the and a the of ADP-ribosylation of domain and the which is very the in of in The tip of domain the diphthamide and the in domain Å the conformation of ADP-ribosylation in domain IV, which domain This that that the of the of structure contains which in of of GDP in for and We have for that is the ADP-ribosylation in domain at a the domain a in the the GDP in have been of the of for GDP show that the of yeast in show that of in the presence of is the presence of the This is the of in the that the diphthamide the tip of domain is the of and that the of the diphthamide has been that ADP-ribosylation of a of for and that a for the is the of the is that the ADP-ribose the the and of in of ADP-ribosylation the of The for and GDP yeast in for both and in the of the for GDP is for that the of for and GDP is ADP-ribosylation showing the for of structure is that the ADP-ribose is that the the diphthamide is for of a both the and the diphthamide the the of domain in the ADP-ribose the of in the of and ADP-ribosylation of the in structure is that in the and for the is that the in an as for in in of the This an for and for the of the ADP-ribosylation the of the is for a the of the the diphthamide for the of for the in the of the of the ADP-ribose structure confirms that the the in an inversion of configuration at of the as toxin and have been inversion of configuration for the which that a and and ADP-ribosylation of which that the This is in the that the crystal of sordarin the sordarin the of of the the of sordarin in the the and and the of the diphthamide and the of the ADP-ribosylation at a elongation factor 2 elongation factor exotoxin ADP-ribosylated elongation factor elongation aeruginosa exotoxin a electron elongation factor exotoxin ADP-ribosylated elongation factor elongation aeruginosa exotoxin a electron the in the elongation of in the is the the and the is the the the for the crystal structure of yeast in the presence and of the sordarin This structure of the inhibitor the of the This is of both and the the showing that the IV, and and have that in and that both a and of domain in a in that and as domain for and This is in the in of the in contains a which a as diphthamide This residue is at in domain of yeast of in the have that the residue is the and This has the that the tip of domain the diphthamide have a in the the is in and is and of diphthamide at experiments the diphthamide have that the diphthamide residue is for The diphthamide of is the for diphtheria toxin and Pseudomonas aeruginosa exotoxin which both the of ADP-ribose at the diphthamide in of the in a and and of the and and that the a an This is the inversion of configuration for the glycosidic the and diphthamide The inversion is the of the a the in diphthamide have that in the of diphthamide both diphtheria toxin and and has as an residue the crystal structure of that is a the of domain that is the of that is the ADP-ribosylation of and of the of the structure of domain of exotoxin in the that and of the a in and a of and diphtheria has been The the ADP-ribose of the diphthamide residue of and This that the diphthamide residue is a of and is a target for has been that the the toxin in that a of the the and that the of the in the of in toxin and the of the ADP-ribosylation of is and for the in We have the structure of ADP-ribosylated diphthamide in yeast and in GDP and the inhibitor The crystal structure the inversion of configuration of the of the of and of the diphthamide residue the structure that the in and the in is the in the that the of the diphthamide is the at the The structure of the the electron density for the diphthamide structure of contains electron density for GDP and which in a of the in the the of GDP We showing that has the domain of as is that both and and GDP and in show that yeast a yeast and the for sordarin The structure of the ADP-ribosylated diphthamide is the first structure showing the conformation of an ADP-ribose covalently attached a target residue and the of ADP-ribosylation and the the elongation of the that is of the the a of of as The of a and as of of of in and The a at for the and a in The a The a in and a and of and a residue the and both and as Binding as The for determined the as of the of is the in for is the in at of the is the for the of and is the of of Binding of and sordarin in the of of the as a of a of in the presence of at in an of of at and the at in a The and for for the and the the The for the factor the factor for sordarin determined the as for the sordarin the Binding the of a of in of The for and a of a in and at for The in and of in sordarin as the very in a a for of both and at The and and and in of the ADP-ribosylated diphthamide the which and and for The ADP-ribosylated diphthamide of in and the density The structure and and the in The and structure for the structure of ADP-ribosylated at the the at the at in in for for the of a of and the and structure factor and is a factor. is a of in The as for the determined structure at Å and at the at in in for for the of a and the and structure factor and is a is a of in The as for the determined structure at Å in a of as The of a and as of of of in and The a at for the and a in The a The a in and a and of and a residue the and both and as Binding as The for determined the as of the of is the in for is the in at of the is the for the of and is the of of Binding of and sordarin in the of of the as a of a of in the presence of at in an of of at and the at in a The and for for the and the the The for the factor the factor for sordarin determined the as for the sordarin the Binding the of a of in of The for and a of a in and at for The in and of in sordarin as the very in a a for of both and at The and and and in of the ADP-ribosylated diphthamide the which and and for The ADP-ribosylated diphthamide of in and the density The structure and and the in The and structure for the structure of ADP-ribosylated at the the of and the the and in the of This that the of the the of of the for the The of for a This the the in and the the the determined and for the and presence of the the the toxin for that the of the The a The of the for in a the and of for the the ADP-ribosylated of and a the the and the and a of the The of and that at a have determined the for and GDP yeast of GDP in the of the of the of the at of of the and the of for and GDP show that ADP-ribosylation of has very for the and that in for and The of in for and for the and which the experiments as yeast ADP-ribose for determined experiments as yeast ADP-ribose for determined in a structure of in the inhibitor and as for the structure sordarin in a IV, and The for sordarin yeast in the of determined in of the of the at of and is for sordarin which the that the sordarin the of a of 2.6 Å in and sordarin The the of in sordarin and GDP the of the the structure the crystal and the the structure an map that electron density for the ADP-ribose and and and of the a of Å The ADP-ribosylation at the is in the electron density map the and the for a the density the the density for the first and in and the map density for the which has of the ADP-ribose electron density and the in electron density map density for the diphthamide attached the at the of the electron density for the is density for the and in the density of and the diphthamide and in an of and an of density for the in the electron density map that the The the attached the of the electron density map an inversion of configuration of the the and the the in The ADP-ribosylated diphthamide is at the tip of domain the ADP-ribose a of the crystal a the of the The and a of the of the attached the of the diphthamide. the which the in that The of the ADP-ribose have the diphthamide is in a the ADP-ribose and and of a in the crystal Å the The of the diphthamide is Å at the of the the diphthamide is Å at of GDP Binding electron density map the of GDP and very density for GDP for the GDP is in a the and and in and in and in the and in the the and and density at the is as an and is and the of the an as in the density for is the of GDP and structure contains a of in the for the in the has is in the and of GDP and GDP of the electron density map GDP and a of the structure GDP and and at GDP and in the the and The map is a GDP and a and and at the and the at in the the Å of the and and the GDP structure of and the the and in the of This that the of the the of of the for the The of for a This the the in and the the the determined and for the and presence of the the the toxin for that the of the The a The of the for in a the and of for the the ADP-ribosylated of and a the the and the and a of the The of and that at a GDP have determined the for and GDP yeast of GDP in the of the of the of the at of of the and the of for and GDP show that ADP-ribosylation of has very for the and that in for and The of in for and for the and which the structure of in the inhibitor and as for the structure sordarin in a IV, and The for sordarin yeast in the of determined in of the of the at of and is for sordarin which the that the sordarin the of a of 2.6 Å in and sordarin The the of in sordarin and GDP the of the the structure the crystal and the the structure an map that electron density for the ADP-ribose The and and and of the a of Å The ADP-ribosylation at the is in the electron density map the and the for a the density the the density for the first and in and the map density for the which has of the ADP-ribose electron density and the in electron density map density for the diphthamide attached the at the of the electron density for the is density for the and in the density of and the diphthamide and in an of and an of density for the in the electron density map that the The the attached the of the electron density map an inversion of configuration of the the and the the in The ADP-ribosylated diphthamide is at the tip of domain the ADP-ribose a of the crystal a the of the The and a of the of the attached the of the diphthamide. the which the in that The of the ADP-ribose have the The diphthamide is in a the ADP-ribose and and of a in the crystal Å the The of the diphthamide is Å at the of the the diphthamide is Å at resolution. of GDP Binding electron density map the of GDP and very density for GDP for the GDP is in a the and and in and in and in the and in the the and and density at the is as an and is and the of the an as in the density for is the of GDP and structure contains a of in the for the in the has is in the and of GDP and ADP-ribosylation of a of both and a very in and of the the and of and and Pseudomonas in which an as a a for of both the and of target have been has determined the structure of the of the as the for structure is the first of ADP-ribosylated and that the is attached the diphthamide of is and the the sordarin of of is and of of the at the of domain is and in both of that the presence of sordarin the and the of the in show that the conformation of IV, and is the ADP-ribosylation the of the the ADP-ribosylated is of of translation ADP-ribosylation of is experiments have that and ADP-ribosylation This that in the of the of the This and which has been for a very in have a in the of the as as a in and of ADP-ribosylation a the of that ADP-ribosylation of the of in the of a of of the and a the of ADP-ribosylation of domain and the which is very the in of in The tip of domain the diphthamide and the in domain Å the conformation of ADP-ribosylation in domain IV, which domain This that that the of the of structure contains which in of of GDP in for and We have for that is the ADP-ribosylation in domain at a the domain a in the the GDP in have been of the of for GDP show that the of yeast in show that of in the presence of is the presence of the This is the of in the that the diphthamide the tip of domain is the of and that the of the diphthamide has been that ADP-ribosylation of a of for and that a for the is the of the is that the ADP-ribose the the and of in of ADP-ribosylation the of The for and GDP yeast in for both and in the of the for GDP is for that the of for and GDP is ADP-ribosylation showing the for of structure is that the ADP-ribose is that the the diphthamide is for of a both the and the diphthamide the the of domain in the ADP-ribose the of in the of and ADP-ribosylation of the in structure is that in the and for the is that the in an as for in in of the This an for and for the of the ADP-ribosylation the of the is for a the of the the diphthamide for the of for the in the of the of the ADP-ribose structure confirms that the the in an inversion of configuration at of the as toxin and have been inversion of configuration for the which that a and and ADP-ribosylation of which that the This is in the that the crystal of sordarin the sordarin the of of the the of sordarin in the the and and the of the diphthamide and the of the ADP-ribosylation at a The ADP-ribosylation of a of both and a very in and of the the and of and and Pseudomonas in which an as a a for of both the and of target have been has determined the structure of the of the as the for structure is the first of ADP-ribosylated and that the is attached the diphthamide of is and the We the sordarin of of is and of of the at the of domain is and in both of that the presence of sordarin the and the of the in show that the conformation of IV, and is the ADP-ribosylation the of the the ADP-ribosylated is The of of translation ADP-ribosylation of is experiments have that and ADP-ribosylation This that in the of the of the This and which has been for a very in have a in the of the as as a in and of ADP-ribosylation a the of that ADP-ribosylation of the of in the of a of of the and a the of ADP-ribosylation of domain and the which is very the in of in The tip of domain the diphthamide and the in domain Å the conformation of ADP-ribosylation in domain IV, which domain This that that the of the of The structure contains which in of of GDP in for and We have for that is the ADP-ribosylation in domain at a the domain a in the the GDP in have been of the of for GDP show that the of yeast in show that of in the presence of is the presence of the This is the of in the that the diphthamide the tip of domain is the of and that the of the diphthamide has been that ADP-ribosylation of a of for and that a for the is the of the is that the ADP-ribose the the and of in of ADP-ribosylation the of The for and GDP yeast in for both and in the of the for GDP is for that the of for and GDP is ADP-ribosylation showing the for of structure is that the ADP-ribose is that the the diphthamide is for of a both the and the diphthamide the the of domain in the ADP-ribose the of in the of and ADP-ribosylation of the in structure is that in the and for the is that the in an as for The in in of the This an for and for the of the ADP-ribosylation the of the is for a the of the the diphthamide for the of for the in the of the of the ADP-ribose structure confirms that the the in an inversion of configuration at of the as toxin and have been inversion of configuration for the which that a The and and ADP-ribosylation of which that the This is in the that the crystal of sordarin the sordarin the of of the the of sordarin in the the and and the of the diphthamide and the of the ADP-ribosylation at a We for and at for

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.