1sr4
From Proteopedia
Crystal Structure of the Haemophilus ducreyi cytolethal distending toxin
Structural highlights
FunctionCDTA_HAEDU CDTs are cytotoxins which induce host cell distension, growth arrest in G2/M phase, nucleus swelling, and chromatin fragmentation in HeLa cells. CdtA, along with CdtC, probably forms a heterodimeric subunit required for the delivery of CdtB. 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 PubMedThe tripartite cytolethal distending toxin (CDT) induces cell cycle arrest and apoptosis in eukaryotic cells. The subunits CdtA and CdtC associate with the nuclease CdtB to form a holotoxin that translocates CdtB into the host cell, where it acts as a genotoxin by creating DNA lesions. Here we show that the crystal structure of the holotoxin from Haemophilus ducreyi reveals that CDT consists of an enzyme of the DNase-I family, bound to two ricin-like lectin domains. CdtA, CdtB and CdtC form a ternary complex with three interdependent molecular interfaces, characterized by globular, as well as extensive non-globular, interactions. The lectin subunits form a deeply grooved, highly aromatic surface that we show to be critical for toxicity. The holotoxin possesses a steric block of the CdtB active site by means of a non-globular extension of the CdtC subunit, and we identify putative DNA binding residues in CdtB that are essential for toxin activity. Assembly and function of a bacterial genotoxin.,Nesic D, Hsu Y, Stebbins CE Nature. 2004 May 27;429(6990):429-33. PMID:15164065[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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