Estrogen Receptor Complexed to
Tamoxifin
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I. Introduction
Estrogen
Receptor
The estrogen receptor regulates
the differentiation and maintenance of neural, skeletal,
cardiovascular, and reproductive tissues in the body. The
ligand binding domain is located in the C-terminus of the protein
and binds estrogen and some synthetic materials, including estrogen
diethylstilbestrol (DES). The protein is composed of 12
α-helices and 2
anti-parallel β-sheets.
This model is of one of the monomers of the estrogen receptor,
but in the body, the protein has biological activity when it is a
dimer.
For more information see
Biochemistry Online:
Chapter
8B - BB: BIOLOGICAL OXIDATION REACTIONS DEHYDROGENASES, MONO- AND DIOXYGENASES,
AND OXIDASES
II. General Structure
Wireframe
Backbone
Backbone and sidechains
Cartoon
Cartoon
, Hbonds and Wireframe
III. Estrogen Receptor with
Tamoxifin
The estrogen receptor can also bind 4-hydroxytamoxifen (tamoxifen), which is a selective estrogen receptor
modulators (SERMs). SERMs act as an antagonist in specific
tissue and promoter contexts by mimicking the interactions of the NR
box peptide with the ligand binding domain. The tamoxifin binds differently
to the receptor complex by changing the binding domain of
α helices 3, 4, 5, and 12.
The
structure of tamoxifen is mostly a hydrophobic hydrocarbon substrate
with a hydrophilic hydroxyl group on it. As a result, most of
the binding residues for tamoxifen have non-polar side chains.
The most common residues that interacted with the hydrophobic part
of the substrate were glycine, leucine, isoleucine, methionine,
alanine, tryptophan, and threonine. The polar residues that
interacted with the polar hydroxyl group of the substrate were
glutamic acid, arginine, and histidine.
Tamoxifin
Tamoxifin
with protein
Critical binding residues of Tamoxifin binding domain
(Met-343, Leu-346, Thr-347, Glu-353, Trp-383, Leu-384, Leu-387, Arg-394, Met-421, Ile-424,
Gly-521, His-524, Leu-525).
Critical non-polar binding residues of Tamoxifin binding domain (Met-343, Leu-346, Thr-347, Trp-383, Leu-384, Leu-387, Met-421, Ile-424,
Gly-521, Leu-525).
Critical polar binding residues of Tamoxifin binding domain
(Glu-353, Arg-394, His-524)
Cartoon with Tamoxifin binding domain
Data for this molecule was obtained from Estrogen
Receptor Complexed to DES and tamoxifen. Cell v95 pp.927-937,
1998