1lhw
From Proteopedia
(New page: 200px<br /> <applet load="1lhw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lhw, resolution 1.75Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1lhw.gif|left|200px]]<br /> | + | [[Image:1lhw.gif|left|200px]]<br /><applet load="1lhw" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1lhw" size=" | + | |
caption="1lhw, resolution 1.75Å" /> | caption="1lhw, resolution 1.75Å" /> | ||
'''CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 2-METHOXYESTRADIOL'''<br /> | '''CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 2-METHOXYESTRADIOL'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In a crystal structure of the amino-terminal laminin G-like domain of | + | 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== | ==About this Structure== | ||
| - | 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 CA, ESM and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Avvakumov, G | + | [[Category: Avvakumov, G V.]] |
[[Category: Grishkovskaya, I.]] | [[Category: Grishkovskaya, I.]] | ||
| - | [[Category: Hammond, G | + | [[Category: Hammond, G L.]] |
| - | [[Category: Muller, Y | + | [[Category: Muller, Y A.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: ESM]] | [[Category: ESM]] | ||
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[[Category: shbg]] | [[Category: shbg]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:45:06 2008'' |
Revision as of 11:45, 21 February 2008
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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 with , and as ligands. 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
Page seeded by OCA on Thu Feb 21 13:45:06 2008
Categories: Homo sapiens | Single protein | Avvakumov, G V. | Grishkovskaya, I. | Hammond, G L. | Muller, Y A. | CA | ESM | IPA | 2-methoxyestradiol | Shbg
