1lhw

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[[Image:1lhw.gif|left|200px]]<br /><applet load="1lhw" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1lhw.gif|left|200px]]
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caption="1lhw, resolution 1.75&Aring;" />
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'''CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 2-METHOXYESTRADIOL'''<br />
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{{Structure
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|PDB= 1lhw |SIZE=350|CAPTION= <scene name='initialview01'>1lhw</scene>, resolution 1.75&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ESM:1,3,5(10)-ESTRATRIEN-2,3,17-BETA-TRIOL+2-METHYL+ETHER'>ESM</scene> and <scene name='pdbligand=IPA:ISOPROPYL ALCOHOL'>IPA</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 2-METHOXYESTRADIOL'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1LHW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=ESM:'>ESM</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LHW OCA].
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1LHW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LHW OCA].
==Reference==
==Reference==
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Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol., Avvakumov GV, Grishkovskaya I, Muller YA, Hammond GL, J Biol Chem. 2002 Nov 22;277(47):45219-25. Epub 2002 Sep 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12228253 12228253]
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Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol., Avvakumov GV, Grishkovskaya I, Muller YA, Hammond GL, J Biol Chem. 2002 Nov 22;277(47):45219-25. Epub 2002 Sep 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12228253 12228253]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: shbg]]
[[Category: shbg]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:45:06 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:31:03 2008''

Revision as of 10:31, 20 March 2008

Image:1lhw.gif


PDB ID 1lhw

Drag the structure with the mouse to rotate
, resolution 1.75Å
Ligands: , and
Coordinates: save as pdb, mmCIF, xml



CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 2-METHOXYESTRADIOL


Overview

In a crystal structure of the amino-terminal laminin G-like domain of human sex hormone-binding globulin (SHBG), the biologically active estrogen metabolite, 2-methoxyestradiol (2-MeOE2), binds in the same orientation as estradiol. The high affinity of SHBG for 2-MeOE2 relies primarily on hydrogen bonding between the hydroxyl at C-3 of 2-MeOE2 and Asp(65) and an interaction between the methoxy group at C-2 and the amido group of Asn(82). Accommodation of the 2-MeOE2 methoxy group causes an outward displacement of residues Ser(128)-Pro(130), which appears to disorder and displace the loop region (Leu(131)-His(136)) that covers the steroid-binding site. This could influence the binding kinetics of 2-MeOE2 and/or facilitate ligand-dependent interactions between SHBG and other proteins. Occupancy of a zinc-binding site reduces the affinity of SHBG for 2-MeOE2 and estradiol in the same way. The higher affinity of SHBG for estradiol derivatives with a halogen atom at C-2 is due to either enhanced hydrogen bonding between the hydroxyl at C-3 and Asp(65) (2-fluoroestradiol) or accommodation of the functional group at C-2 (2-bromoestradiol), rather than an interaction with Asn(82). By contrast, the low affinity of SHBG for 2-hydroxyestradiol can be attributed to intra-molecular hydrogen bonding between the hydroxyls in the aromatic steroid ring A, which generates a steric clash with the amido group of Asn(82). Understanding how C-2 derivatives of estradiol interact with SHBG could facilitate the design of biologically active synthetic estrogens.

About this Structure

1LHW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human sex hormone-binding globulin in complex with 2-methoxyestradiol reveals the molecular basis for high affinity interactions with C-2 derivatives of estradiol., Avvakumov GV, Grishkovskaya I, Muller YA, Hammond GL, J Biol Chem. 2002 Nov 22;277(47):45219-25. Epub 2002 Sep 11. PMID:12228253

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