2ama: Difference between revisions
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[[Image:2ama.gif|left|200px]] | [[Image:2ama.gif|left|200px]] | ||
'''Crystal structure of human androgen receptor ligand binding domain in complex with dihydrotestosterone''' | {{Structure | ||
|PDB= 2ama |SIZE=350|CAPTION= <scene name='initialview01'>2ama</scene>, resolution 1.90Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=DHT:DIHYDROTESTOSTERONE'>DHT</scene> | |||
|ACTIVITY= | |||
|GENE= AR, DHTR, NR3C4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal structure of human androgen receptor ligand binding domain in complex with dihydrotestosterone''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2AMA is a [ | 2AMA 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=2AMA OCA]. | ||
==Reference== | ==Reference== | ||
Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity., Pereira de Jesus-Tran K, Cote PL, Cantin L, Blanchet J, Labrie F, Breton R, Protein Sci. 2006 May;15(5):987-99. PMID:[http:// | Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity., Pereira de Jesus-Tran K, Cote PL, Cantin L, Blanchet J, Labrie F, Breton R, Protein Sci. 2006 May;15(5):987-99. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16641486 16641486] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
''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 15:51:16 2008'' | ||
Revision as of 16:51, 20 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | AR, DHTR, NR3C4 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human androgen receptor ligand binding domain in complex with dihydrotestosterone
OverviewOverview
Androgens exert their effects by binding to the highly specific androgen receptor (AR). In addition to natural potent androgens, AR binds a variety of synthetic agonist or antagonist molecules with different affinities. To identify molecular determinants responsible for this selectivity, we have determined the crystal structure of the human androgen receptor ligand-binding domain (hARLBD) in complex with two natural androgens, testosterone (Testo) and dihydrotestosterone (DHT), and with an androgenic steroid used in sport doping, tetrahydrogestrinone (THG), at 1.64, 1.90, and 1.75 A resolution, respectively. Comparison of these structures first highlights the flexibility of several residues buried in the ligand-binding pocket that can accommodate a variety of ligand structures. As expected, the ligand structure itself (dimension, presence, and position of unsaturated bonds that influence the geometry of the steroidal nucleus or the electronic properties of the neighboring atoms, etc.) determines the number of interactions it can make with the hARLBD. Indeed, THG--which possesses the highest affinity--establishes more van der Waals contacts with the receptor than the other steroids, whereas the geometry of the atoms forming electrostatic interactions at both extremities of the steroid nucleus seems mainly responsible for the higher affinity measured experimentally for DHT over Testo. Moreover, estimation of the ligand-receptor interaction energy through modeling confirms that even minor modifications in ligand structure have a great impact on the strength of these interactions. Our crystallographic data combined with those obtained by modeling will be helpful in the design of novel molecules with stronger affinity for the AR.
DiseaseDisease
Known diseases associated with this structure: Androgen insensitivity OMIM:[313700], Breast cancer, male, with Reifenstein syndrome OMIM:[313700], Hypospadias, perineal OMIM:[313700], Prostate cancer OMIM:[313700], Prostate cancer, susceptibility to OMIM:[313700], Spinal and bulbar muscular atrophy of Kennedy OMIM:[313700]
About this StructureAbout this Structure
2AMA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity., Pereira de Jesus-Tran K, Cote PL, Cantin L, Blanchet J, Labrie F, Breton R, Protein Sci. 2006 May;15(5):987-99. PMID:16641486
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