1ltg
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THE ARG7LYS MUTANT OF HEAT-LABILE ENTEROTOXIN EXHIBITS GREAT FLEXIBILITY OF ACTIVE SITE LOOP 47-56 OF THE A SUBUNIT
OverviewOverview
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 StructureAbout this Structure
1LTG is a Protein complex structure of sequences from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
The Arg7Lys mutant of heat-labile enterotoxin exhibits great flexibility of active site loop 47-56 of the A subunit., van den Akker F, Merritt EA, Pizza M, Domenighini M, Rappuoli R, Hol WG, Biochemistry. 1995 Sep 5;34(35):10996-1004. PMID:7669757
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