1ltg: Difference between revisions

Line 1:

[[Image:1ltg.gif|left|200px]]<br /><applet load="1ltg" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1ltg.gif|left|200px]]<br /><applet load="1ltg" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1ltg, resolution 2.4Å" />

'''THE ARG7LYS MUTANT OF HEAT-LABILE ENTEROTOXIN EXHIBITS GREAT FLEXIBILITY OF ACTIVE SITE LOOP 47-56 OF THE A SUBUNIT'''<br />

==Overview==

The heat-labile enterotoxin from Escherichia coli (LT) is a member of the, cholera toxin family. These and other members of the larger class of AB5, bacterial toxins act through catalyzing the ADP-ribosylation of various, intracellular targets including Gs alpha. The A subunit is responsible for, this covalent modification, while the B pentamer is involved in receptor, recognition. We report here the crystal structure of an inactive, single-site mutant of LT in which arginine 7 of the A subunit has been, replaced by a lysine residue. The final model contains 103 residues for, each of the five B subunits, 175 residues for the A1 subunit, and 41, residues for the A2 subunit. In this Arg7Lys structure the active site, cleft within the A subunit is wider by approximately 1 A than is seen in, the wild-type LT. Furthermore, a loop near the active site consisting of, residues 47-56 is disordered in the Arg7Lys structure, even though the new, lysine residue at position 7 assumes a position which virtually coincides, with that of Arg7 in the wild-type structure. The displacement of residues, 47-56 as seen in the mutant structure is proposed to be necessary for, allowing NAD access to the active site of the wild-type LT. On the basis, of the differences observed between the wild-type and Arg7Lys structures, we propose a model for a coordinated sequence of conformational changes, required for full activation of LT upon reduction of disulfide bridge, 187-199 and cleavage of the peptide loop between the two cysteines in the, A subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

The heat-labile enterotoxin from Escherichia coli (LT) is a member of the cholera toxin family. These and other members of the larger class of AB5 bacterial toxins act through catalyzing the ADP-ribosylation of various intracellular targets including Gs alpha. The A subunit is responsible for this covalent modification, while the B pentamer is involved in receptor recognition. We report here the crystal structure of an inactive single-site mutant of LT in which arginine 7 of the A subunit has been replaced by a lysine residue. The final model contains 103 residues for each of the five B subunits, 175 residues for the A1 subunit, and 41 residues for the A2 subunit. In this Arg7Lys structure the active site cleft within the A subunit is wider by approximately 1 A than is seen in the wild-type LT. Furthermore, a loop near the active site consisting of residues 47-56 is disordered in the Arg7Lys structure, even though the new lysine residue at position 7 assumes a position which virtually coincides with that of Arg7 in the wild-type structure. The displacement of residues 47-56 as seen in the mutant structure is proposed to be necessary for allowing NAD access to the active site of the wild-type LT. On the basis of the differences observed between the wild-type and Arg7Lys structures, we propose a model for a coordinated sequence of conformational changes required for full activation of LT upon reduction of disulfide bridge 187-199 and cleavage of the peptide loop between the two cysteines in the A subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

==About this Structure==

1LTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1LTG OCA].

1LTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LTG OCA].

==Reference==

Line 13:

[[Category: Escherichia coli]]

[[Category: Protein complex]]

[[Category: Akker, F.Van.Den.]]

[[Category: Akker, F Van Den.]]

[[Category: Hol, W.G.J.]]

[[Category: Hol, W G.J.]]

[[Category: enterotoxin]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Tue Nov 20 20~~:52:~~02 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:16 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:1ltg.gif|left|200px]]<br /><applet load="1ltg" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ltg.gif|left|200px]]<br /><applet load="1ltg" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ltg, resolution 2.4&Aring;" />
 '''THE ARG7LYS MUTANT OF HEAT-LABILE ENTEROTOXIN EXHIBITS GREAT FLEXIBILITY OF ACTIVE SITE LOOP 47-56 OF THE A SUBUNIT'''<br />
 ==Overview==
-The heat-labile enterotoxin from Escherichia coli (LT) is a member of the, cholera toxin family. These and other members of the larger class of AB5, bacterial toxins act through catalyzing the ADP-ribosylation of various, intracellular targets including Gs alpha. The A subunit is responsible for, this covalent modification, while the B pentamer is involved in receptor, recognition. We report here the crystal structure of an inactive, single-site mutant of LT in which arginine 7 of the A subunit has been, replaced by a lysine residue. The final model contains 103 residues for, each of the five B subunits, 175 residues for the A1 subunit, and 41, residues for the A2 subunit. In this Arg7Lys structure the active site, cleft within the A subunit is wider by approximately 1 A than is seen in, the wild-type LT. Furthermore, a loop near the active site consisting of, residues 47-56 is disordered in the Arg7Lys structure, even though the new, lysine residue at position 7 assumes a position which virtually coincides, with that of Arg7 in the wild-type structure. The displacement of residues, 47-56 as seen in the mutant structure is proposed to be necessary for, allowing NAD access to the active site of the wild-type LT. On the basis, of the differences observed between the wild-type and Arg7Lys structures, we propose a model for a coordinated sequence of conformational changes, required for full activation of LT upon reduction of disulfide bridge, 187-199 and cleavage of the peptide loop between the two cysteines in the, A subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
+The heat-labile enterotoxin from Escherichia coli (LT) is a member of the cholera toxin family. These and other members of the larger class of AB5 bacterial toxins act through catalyzing the ADP-ribosylation of various intracellular targets including Gs alpha. The A subunit is responsible for this covalent modification, while the B pentamer is involved in receptor recognition. We report here the crystal structure of an inactive single-site mutant of LT in which arginine 7 of the A subunit has been replaced by a lysine residue. The final model contains 103 residues for each of the five B subunits, 175 residues for the A1 subunit, and 41 residues for the A2 subunit. In this Arg7Lys structure the active site cleft within the A subunit is wider by approximately 1 A than is seen in the wild-type LT. Furthermore, a loop near the active site consisting of residues 47-56 is disordered in the Arg7Lys structure, even though the new lysine residue at position 7 assumes a position which virtually coincides with that of Arg7 in the wild-type structure. The displacement of residues 47-56 as seen in the mutant structure is proposed to be necessary for allowing NAD access to the active site of the wild-type LT. On the basis of the differences observed between the wild-type and Arg7Lys structures, we propose a model for a coordinated sequence of conformational changes required for full activation of LT upon reduction of disulfide bridge 187-199 and cleavage of the peptide loop between the two cysteines in the A subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
 ==About this Structure==
-LTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LTG OCA].
+LTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LTG OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Escherichia coli]]
 [[Category: Protein complex]]
-[[Category: Akker, F.Van.Den.]]
+[[Category: Akker, F Van Den.]]
-[[Category: Hol, W.G.J.]]
+[[Category: Hol, W G.J.]]
 [[Category: enterotoxin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:52:02 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:16 2008''