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Crystal structures of apparent saccharide sensors from histidine kinase receptors prevalent in a human gut symbiont.

ABSTRACT: The adult human gut is a complicated ecosystem in which host-bacterium symbiosis plays an important role. Bacteroides thetaiotaomicron is a predominant member of the gut microflora, providing the human digestive tract with a large number of glycolytic enzymes. Expression of many of these enzymes appears to be controlled by histidine kinase receptors that are fused into unusual hybrid two-component systems that share homologous periplasmic sensor domains. These sensor domains belong to the third most populated (HK3) family based on a previous unpublished bioinformatics analysis of predicted histidine kinase sensors. Here, we present the crystal structures of two sensor domains representative of the HK3 family. Each sensor is folded into three domains: two-seven-bladed ?-propeller domains and one ?-sandwich domain. Both sensors form dimers in crystals, and one sensor appears to be physiologically relevant. The folding characteristics in the individual domains, the domain organization, and the oligomeric architecture are all unique to HK3 sensors. Sequence analysis of the HK3 sensors indicates that these sensor domains are shared among other signaling molecules, implying combinatorial molecular evolution.The structural data for the crystallographic results for HK3 BT4673S and HK3 BT3049S have been deposited in the Protein Data Bank under accession numbers 3OTT and 3V9F, respectively.HK3BT3049S and HK3BT3049S bind by x-ray crystallography (View interaction) HK3BT3049S and HK3BT3049S bind by molecular sieving (View interaction) HK3BT3049S and HK3BT3049S bind by cosedimentation through density gradient (View interaction) HK3BT4673s and HK3BT4673s bind by cosedimentation through density gradient (View interaction) HK3BT4673s and HK3BT4673s bind by molecular sieving (View interaction).

SUBMITTER: Zhang Z

PROVIDER: S-EPMC4169315 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Crystal structures of apparent saccharide sensors from histidine kinase receptors prevalent in a human gut symbiont.

Zhang Zhen Z Liu Qun Q Hendrickson Wayne A WA

The FEBS journal 20140804 18

The adult human gut is a complicated ecosystem in which host-bacterium symbiosis plays an important role. Bacteroides thetaiotaomicron is a predominant member of the gut microflora, providing the human digestive tract with a large number of glycolytic enzymes. Expression of many of these enzymes appears to be controlled by histidine kinase receptors that are fused into unusual hybrid two-component systems that share homologous periplasmic sensor domains. These sensor domains belong to the third ...[more]

PMID: 24995510

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Project description:Histidine acid phosphatases catalyze the transfer of a phosphoryl group from phosphomonoesters to water at acidic pH using an active-site histidine. The histidine acid phosphatase from the category A pathogen Francisella tularensis (FtHAP) has been implicated in intramacrophage survival and virulence, motivating interest in understanding the structure and mechanism of this enzyme. Here, we report a structure-based study of ligand recognition by FtHAP. The 1.70-A-resolution structure of FtHAP complexed with the competitive inhibitor l(+)-tartrate was solved using single-wavelength anomalous diffraction phasing. Structures of the ligand-free enzyme and the complex with inorganic phosphate were determined at resolutions of 1.85 and 1.70 A, respectively. The structure of the Asp261Ala mutant enzyme complexed with the substrate 3'-AMP was determined at 1.50 A resolution to gain insight into substrate recognition. FtHAP exhibits a two-domain fold similar to that of human prostatic acid phosphatase, consisting of an alpha/beta core domain and a smaller domain that caps the core domain. The structures show that the core domain supplies the phosphoryl binding site, catalytic histidine (His17), and an aspartic acid residue (Asp261) that protonates the leaving group, while the cap domain contributes residues that enforce substrate preference. FtHAP and human prostatic acid phosphatase differ in the orientation of the crucial first helix of the cap domain, implying differences in the substrate preferences of the two enzymes. 3'-AMP binds in one end of a 15-A-long tunnel, with the adenine clamped between Phe23 and Tyr135, and the ribose 2'-hydroxyl interacting with Gln132. The importance of the clamp is confirmed with site-directed mutagenesis; mutation of Phe23 and Tyr135 individually to Ala increases K(m) by factors of 7 and 10, respectively. The structural data are consistent with a role for FtHAP in scavenging phosphate from small molecules present in host macrophage cells.

Dataset Information

Crystal structures of apparent saccharide sensors from histidine kinase receptors prevalent in a human gut symbiont.

Publications

Crystal structures of apparent saccharide sensors from histidine kinase receptors prevalent in a human gut symbiont.

Similar Datasets

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