1i5r
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1i5r.gif|left|200px]] | + | [[Image:1i5r.gif|left|200px]] |
| - | + | ||
| - | '''TYPE 1 17-BETA HYDROXYSTEROID DEHYDROGENASE EM1745 COMPLEX''' | + | {{Structure |
| + | |PDB= 1i5r |SIZE=350|CAPTION= <scene name='initialview01'>1i5r</scene>, resolution 1.6Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=HYC:O5'-[9-(3,17B-DIHYDROXY-1,3,5(10)-ESTRATRIEN-16B-YL)-NONANOYL]ADENOSINE'>HYC</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''TYPE 1 17-BETA HYDROXYSTEROID DEHYDROGENASE EM1745 COMPLEX''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1I5R is a [ | + | 1I5R 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=1I5R OCA]. |
==Reference== | ==Reference== | ||
| - | A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity., Qiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX, FASEB J. 2002 Nov;16(13):1829-31. Epub 2002 Sep 5. PMID:[http:// | + | A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity., Qiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX, FASEB J. 2002 Nov;16(13):1829-31. Epub 2002 Sep 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12223444 12223444] |
[[Category: Estradiol 17-beta-dehydrogenase]] | [[Category: Estradiol 17-beta-dehydrogenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 26: | Line 35: | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:45:55 2008'' |
Revision as of 09:45, 20 March 2008
| |||||||
| , resolution 1.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Estradiol 17-beta-dehydrogenase, with EC number 1.1.1.62 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
TYPE 1 17-BETA HYDROXYSTEROID DEHYDROGENASE EM1745 COMPLEX
Overview
Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 1) catalyzes the final step in the synthesis of active estrogens that stimulate the proliferation of breast cancer cells. Based on the initial premise to make use of the binding energies of both the substrate and cofactor sites, and molecular modeling starting from the enzyme structure, several estradiol-adenosine hybrids were designed and synthesized. Among these hybrids, EM-1745 with a linker of 8-CH2 groups is proved to be the best competitive inhibitor with a Ki of 3.0 +/- 0.8 nM. The crystal structure of the EM-1745 enzyme complex at 1.6 A provides evidence at atomic resolution of strong interactions between both the steroid and cofactor moieties and the enzyme molecule, as illustrated by a deltaA-weighted 2Fo-Fc electron density map contoured at 3.0 delta. The substrate entry loop is further stabilized in this complex compared with previous complexes of the enzyme. These results confirm our initial strategy of combining studies of structural biology and enzyme mechanism in the inhibitor design, which may be applied to other steroidogenic enzymes involved in human diseases.
About this Structure
1I5R is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity., Qiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX, FASEB J. 2002 Nov;16(13):1829-31. Epub 2002 Sep 5. PMID:12223444
Page seeded by OCA on Thu Mar 20 11:45:55 2008
