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Structural basis for agonism and antagonism for a set of chemically related progesterone receptor modulators.

ABSTRACT: The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we present a third progesterone receptor ligand binding domain dimer bound to an agonist in monomer A and an antagonist in monomer B, which display binding modes in agreement with the earlier observation that agonists and antagonists from this series adopt different binding modes.

SUBMITTER: Lusher SJ

PROVIDER: S-EPMC3186393 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Structural basis for agonism and antagonism for a set of chemically related progesterone receptor modulators.

Lusher Scott J SJ Raaijmakers Hans C A HC Vu-Pham Diep D Dechering Koen K Lam Tsang Wai TW Brown Angus R AR Hamilton Niall M NM Nimz Olaf O Bosch Rolien R McGuire Ross R Oubrie Arthur A de Vlieg Jacob J

The Journal of biological chemistry 20110817 40

The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we pr ...[more]

PMID: 21849509

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