1ENH and 1ZTR
1ENH: Native Drosophila melanogaster engrailed homeodomain
1ZTR: Denatured Drosophila melanogaster engrailed homeodomain mutant L16A
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from the fruit fly Drosophila melanogaster, is a 61-residue,
3-alpha helix bundle protein (H1, H2, H3).
mutant of 1ENH, given the code 1ZTR, directly
solves the solution structure of a true denatured state under conditions
that would typically favor folding.
Denaturation had been encouraged by a L16A mutation in
1ENH. L16A is a fully buried residue located
in the middle of H1. The mutation from leucine to alanine changed the
side chain from a larger hydrophobe to a smaller one, which decreased
van der Waals interactions and decreased protein stability.
in ionic strength cause 1ZTR to fold and unfold reversibly. At high
ionic strengths, the mutant protein exists in its folded, native state,
but at physiological ionic strength
(~ 150 mM) the protein denatures.
The solution structure
of 1ZTR was obtained by 1HNMR. The
above structure of 1ZTR shows a superimposition of the 25 lowest-energy
conformer structures. Only one of these conformer structures was
selected for display in this Jmol.
For more information see
Biochemistry Online: Chapter 2D - PROTEIN FOLDING/STABILITY IN VIVO AND IN VITRO
II. General Structure
Native State (1ENH)
The native state of En-HD is compact in shape
Hydrophobic residues are mostly in the interior of
Denatured State (1ZTR)
Because this structure was determined by
1HNMR, hydrogens show up (as white)
denatured state is larger, more elongated, and less compact than the
H1 is longer
by at least one turn compared to the native state
core is disrupted in the denatured state, the helical structure and the
turn connecting H2 and H3 remains intact
hydrophobic residues are exposed at the surface
Superimposition of 1ENH and 1ZTR
Native state shown in light blue, denatured state shown
L., Markson, J. S., Mayor, U., Freund, S. M. V., Fersht, A. R. Solution
structure of a protein denatured state and folding intermediate.
Nature 437, 1053-1056 (13 October 2005).