2gpz
From Proteopedia
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Transthyretin-like protein from Salmonella dublin
Overview
The mechanism of binding of thyroid hormones by the transport protein, transthyretin (TTR) in vertebrates is structurally well characterised., However, a homologous family of transthyretin-like proteins (TLPs) present, in bacteria as well as eukaryotes do not bind thyroid hormones, instead, they are postulated to perform a role in the purine degradation pathway, and function as 5-hydroxyisourate hydrolases. Here we describe the 2.5, Angstroms X-ray crystal structure of the TLP from the Gram-negative, bacterium Salmonella dublin, and compare and contrast its structure with, vertebrate TTRs. The overall architecture of the homotetramer is conserved, and, despite low sequence homology with vertebrate TTRs, structural, differences within the monomer are restricted to flexible loop regions., However, sequence variation at the dimer-dimer interface has profound, consequences for the ligand binding site and provides a structural, rationalisation for the absence of thyroid hormone binding affinity in, bacterial TLPs: the deep, negatively charged thyroxine-binding pocket that, characterises vertebrate TTR contrasts with a shallow and elongated, positively charged cleft in S. dublin TLP. We have demonstrated that, Sdu_TLP is a 5-hydroxyisourate hydrolase. Furthermore, using site-directed, mutagenesis, we have identified three conserved residues located in this, cleft that are critical to the enzyme activity. Together our data reveal, that the active site of Sdu_TLP corresponds to the thyroxine binding site, in TTRs.
About this Structure
2GPZ is a Single protein structure of sequence from Salmonella enterica subsp. enterica serovar dublin with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
The crystal structure of the transthyretin-like protein from Salmonella dublin, a prokaryote 5-hydroxyisourate hydrolase., Hennebry SC, Law RH, Richardson SJ, Buckle AM, Whisstock JC, J Mol Biol. 2006 Jun 23;359(5):1389-99. Epub 2006 May 11. PMID:16787778
Page seeded by OCA on Wed Nov 21 11:19:59 2007
