1lhw
From Proteopedia
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|PDB= 1lhw |SIZE=350|CAPTION= <scene name='initialview01'>1lhw</scene>, resolution 1.75Å | |PDB= 1lhw |SIZE=350|CAPTION= <scene name='initialview01'>1lhw</scene>, resolution 1.75Å | ||
|SITE= | |SITE= | ||
| - | |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> | + | |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>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1d2s|1D2S]], [[1f5f|1F5F]], [[1kdk|1KDK]], [[1kdm|1KDM]], [[1lhn|1LHN]], [[1lho|1LHO]], [[1lhu|1LHU]], [[1lhv|1LHV]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lhw OCA], [http://www.ebi.ac.uk/pdbsum/1lhw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lhw RCSB]</span> | ||
}} | }} | ||
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[[Category: Hammond, G L.]] | [[Category: Hammond, G L.]] | ||
[[Category: Muller, Y A.]] | [[Category: Muller, Y A.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: ESM]] | ||
| - | [[Category: IPA]] | ||
[[Category: 2-methoxyestradiol]] | [[Category: 2-methoxyestradiol]] | ||
[[Category: shbg]] | [[Category: shbg]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:02:57 2008'' |
Revision as of 19:03, 30 March 2008
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| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Related: | 1D2S, 1F5F, 1KDK, 1KDM, 1LHN, 1LHO, 1LHU, 1LHV
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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