Three-dimensional model for the hormone binding domains of steroid receptors.

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.

authors

Goldstein RA,Katzenellenbogen JA,Luthey-Schulten ZA,Seielstad DA,Wolynes PG

doi

10.1073/pnas.90.21.9949

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

9949-53

issue

21

eissn

0027-8424

issn

1091-6490

journal_volume

90

pub_type

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