2bgc

PRFA-G145S, A CONSTITUTIVE ACTIVE MUTANT OF THE TRANSCRIPTIONAL REGULATOR IN L.MONOCYTOGENES

spinqualitylabelsall models 2bgc, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2bgc is a 8 chain structure with sequence from Lismo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DTT, DTU NonStd Res: PR3 Related: 1omi, 2beo Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Listeria monocytogenes, a Gram-positive, facultative intracellular human pathogen, causes systemic infections with high mortality rate. The majority of the known pathogenicity factors of L. monocytogenes is regulated by a single transcription factor, PrfA. Hyperhaemolytic laboratory strains of L. monocytogenes express the constitutively active mutant PrfA(G145S) inducing virulence gene overexpression independent of environmental conditions. PrfA belongs to the Crp/Fnr family of transcription factors generally activated by a small effector, such as cAMP or O(2). We present the crystal structures of wild-type PrfA, the first Gram-positive member of the Crp/Fnr family, and of the constitutively active mutant PrfA(G145S). Cap (Crp) has previously been described exclusively in the cAMP-induced (DNA-free and -bound) conformation. By contrast, the PrfA structures present views both of the non-induced state and of the mutationally activated form. The low DNA-binding affinity of wild-type PrfA is supported both structurally (partly disordered helix-turn-helix motif, overall geometry of the HTH alpha-helices deviates from Cap) and by surface plasmon resonance analyses (K(D) = 0.9 microM). In PrfA(G145S) the HTH motifs dramatically rearrange to adopt a conformation comparable to cAMP-induced Cap and hence favourable for DNA binding, supported by a DNA-binding affinity of 50 nM. Finally, the hypothesis that wild-type PrfA, like other Crp/Fnr family members, may require an as yet unidentified cofactor for activation is supported by the presence of a distinct tunnel in PrfA, located at the interface of the beta-barrel and the DNA-binding domain. The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif.,Eiting M, Hageluken G, Schubert WD, Heinz DW Mol Microbiol. 2005 Apr;56(2):433-46. PMID:15813735 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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