 |
PDBsum entry 3dmx
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Halogenated benzenes bound within a non-Polar cavity in t4 lysozyme provide examples of i...S and i...Se halogen-Bonding.
|
|
|
Authors
|
|
L.Liu,
W.A.Baase,
B.W.Matthews.
|
|
|
Ref.
|
|
J Mol Biol, 2009,
385,
595-605.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
We showed earlier that the mutation of Leu99 to alanine in bacteriophage T4
lysozyme creates an internal cavity of volume approximately 150 A(3) that binds
benzene and a variety of other ligands. As such, this cavity provides an
excellent target to study protein-ligand interaction. Here, we use
low-temperature crystallography and related techniques to analyze the binding of
halogen-incorporated benzenes typified by C(6)F(5)X, where X=H, F, Cl, Br or I,
and C(6)H(5)X, where X=H or I was also studied. Because of the increased
electron density of fluorine relative to hydrogen, the geometry of binding of
the fluoro compounds can often be determined more precisely than their
hydrogen-containing analogs. All of the ligands bind in essentially the same
plane but the center of the phenyl ring can translate by up to 1.2 A. In no case
does the ligand rotate freely within the cavity. The walls of the cavity consist
predominantly of hydrocarbon atoms, and in several cases it appears that van der
Waals interactions define the geometry of binding. In comparing the smallest
with the largest ligand, the cavity volume increases from 181 A(3) to 245 A(3).
This shows that the protein is flexible and adapts to the size and shape of the
ligand. There is a remarkably close contact of 3.0 A between the iodine atom on
C(6)F(5)I and the sulfur or selenium atom of Met or SeMet102. This interaction
is 1.0 A less than the sum of the van der Waals radii and is a clear example of
a so-called halogen bond. Notwithstanding this close approach, the increase in
binding energy for the halogen bond relative to a van der Waals contact is
estimated to be only about 0.5-0.7 kcal/mol.
|
|
|
|
|
|
|
|
Figure 1.
Fig. 1. Electron density maps showing the location of ligands
bound in the L99A cavity. Maps have amplitudes (F[obs,complex]
– F[obs,L99A]) and phases from the refined structure of L99A.
Resolution as in Table 1; maps contoured at 3.0σ. (a) C[6]H[6],
ligand in dark blue. (b) C[6]F[6], fluorine atoms in green. (c)
C[6]HF[5]. An alternative binding mode, not shown, is rotated
60° clockwise. (d) Stereo figure superimposing the C[6]F[6]
complex (carbon atoms in orange, fluorine in green) on that for
C[6]H[6] (atoms in blue). The side chain of Met102 is at the top
left with the sulfur atom in yellow. All figures were rendered
with PyMOL [http://www.pymol.org].
|
|
Figure 5.
Fig. 5. (a) Maps showing the binding of C[6]F[5]I to
selenium-substituted L99A. The isomorphous difference map has
amplitudes (F[obs,complex] – F[obs,L99A]) and phases from the
refined structure of L99A. It is shown in red, and contoured at
3.0σ. C[6]F[5]I has density for the bound ligand and, due to
the replacement of Met102, with the more electron-dense
selenomethionine (top left). The map based on the anomalous
scattering differences, contoured in green, is contoured at
3.0σ. (b) Electron density maps, as in panel a, for C[6]H[5]I
bound to selenomethionine L99A. The ligand occupies the position
shown as well as one rotated 180°.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
385,
595-605)
copyright 2009.
|
|
|
|
|
|
|
