Abstract:
:We have used a motif-based structural search method to identify structural homologs of the hormone binding domains of the nuclear receptors from among a set of known protein structures and have found the closest similarity with members of the subtilisin-like serine proteases. These proteins consist of an open twisted sheet of parallel beta-strands flanked on both sides by alpha-helices. The alignment with the protease scaffold was refined by using multiple sequence prealignment of different sets of nuclear receptors, and alternative model structures were screened by considering their consistency with the results of biochemical experiments defining the ligand binding pocket. In the most favored model, nearly all of the residues thought to be involved in ligand binding map to a pocket of appropriate dimensions where the subtilisin-like proteases have their active site. The three-dimensional model that we propose for the hormone binding domains of the nuclear receptors provides a framework for the design of experiments to further investigate nuclear receptor structure and function.
journal_name
Proc Natl Acad Sci U S Aauthors
Goldstein RA,Katzenellenbogen JA,Luthey-Schulten ZA,Seielstad DA,Wolynes PGdoi
10.1073/pnas.90.21.9949subject
Has Abstractpub_date
1993-11-01 00:00:00pages
9949-53issue
21eissn
0027-8424issn
1091-6490journal_volume
90pub_type
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