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Colicins kill E. coli by a process that involves binding to a surface receptor, entering the cell, and, finally, intoxicating it. The lethal action of colicin E3 is a specific cleavage in the ribosomal decoding A site. The crystal structure of colicin E3, reported here in a binary complex with its immunity protein (IP), reveals a Y-shaped molecule with the(More)
Several models of agonist binding to G protein-coupled 5-hydroxytryptamine [5-HT] (serotonin) receptors have highlighted the potential importance of highly conserved aromatic residues for ligand binding and agonist efficacy. In this study, we tested these models by constructing and characterizing a number of point mutations of conserved and nonconserved(More)
The neurohypophysial hormone arginine vasopressin (AVP) is a cyclic nonpeptide whose actions are mediated by the stimulation of specific G protein--coupled membrane receptors pharmacologically classified into V1-vascular (V1R), V2-renal (V2R) and V3-pituitary (V3R) AVP receptor subtypes. The random screening of chemical compounds and optimization of lead(More)
Antivirulence agents inhibit the production of disease-causing virulence factors but are neither bacteriostatic nor bactericidal. Antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA) strain USA300, the most widespread community-associated MRSA strain in the United States, were discovered by virtual screening against the response(More)
Echoviruses are enteroviruses that belong to Picornaviridae. Many echoviruses use decay-accelerating factor (DAF) as their cellular receptor. DAF is a glycosylphosphatidyl inositol-anchored complement regulatory protein found on most cell surfaces. It functions to protect cells from complement attack. The cryo-electron microscopy reconstructions of(More)
Whereas arginine vasopressin binds to its receptor subtypes V(1)R and V(2)R with equal affinity of approximately 2 nM, nonpeptide antagonists interact differently with vasopressin receptor subtypes. The V(2)R antagonist binding site was mapped by site-directed mutagenesis at six selected amino acid positions, K100D, A110W, M120V, L175Y, R202S, and F307I,(More)
Staphylococci are a major health threat because of increasing resistance to antibiotics. An alternative to antibiotic treatment is preventing virulence by inhibition of bacterial cell-to-cell communication using the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP). In this work, we identified 2',5-di-O-galloyl-d-hamamelose (hamamelitannin) as a(More)
AVP receptors represent a logical target for drug development. As a new class of therapeutic agents, orally active AVP analogs could be used to treat several human pathophysiological conditions including neurogenic diabetes insipidus, the syndrome of inappropriate secretion of AVP (SIADH), congestive heart failure, arterial hypertension, liver cirrhosis,(More)
The post-translational sulfation of tyrosine residues occurs in numerous secreted and integral membrane proteins and, in many cases, plays a crucial role in controlling the interactions of these proteins with physiological binding partners as well as invading pathogens. Recent advances in our understanding of protein tyrosine sulfation have come about owing(More)
Plasmodium vivax invasion of human erythrocytes requires interaction of the P. vivax Duffy binding protein (PvDBP) with its host receptor, the Duffy antigen (Fy) on the erythrocyte surface. Consequently, PvDBP is a leading vaccine candidate. The binding domain of PvDBP lies in a cysteine-rich portion of the molecule called region II (PvDBPII). PvDBPII(More)