From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2ama.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:2ama.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2ama| PDB=2ama | SCENE= }} | | {{STRUCTURE_2ama| PDB=2ama | SCENE= }} |
| | | | |
| - | '''Crystal structure of human androgen receptor ligand binding domain in complex with dihydrotestosterone'''
| + | ===Crystal structure of human androgen receptor ligand binding domain in complex with dihydrotestosterone=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16641486}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16641486 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_16641486}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 32: |
Line 36: |
| | [[Category: Ligand binding domain]] | | [[Category: Ligand binding domain]] |
| | [[Category: Nuclear receptor]] | | [[Category: Nuclear receptor]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:12:49 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:37:14 2008'' |
Revision as of 10:37, 27 July 2008
Template:STRUCTURE 2ama
Crystal structure of human androgen receptor ligand binding domain in complex with dihydrotestosterone
Template:ABSTRACT PUBMED 16641486
About this Structure
2AMA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:16641486
Page seeded by OCA on Sun Jul 27 13:37:14 2008
