Refined structures of three crystal forms of toxic shock syndrome toxin‐1 and of a tetramutant with reduced activity

Prasad, G.; Radhakrishnan, R.; Mitchell, David; Earhart, C.A.; Dinges, Martin M.; Cook, William J.; Schlievert, P M; Ohlendorf, D.H.

doi:10.1002/pro.5560060610

Cited by 26 publications

(3 citation statements)

References 57 publications

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“…TSST-1 is encoded by tst H gene in the S. aureus mobile genetic element [ 17 ]. TSST-1 structure and regions that interacted with MHC-II and TCR have been investigated extensively [ 10 , 18 , 19 , 20 ]. Mature toxin (194 residues; ~22 kDa) is monomeric in solution and comprises two tightly packed-distinct domains [ 18 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…The N-terminal domain (small domain B) acquires α-helix configuration (α1; residues 1–17) that is surrounded by five β-strands (β1-β5; residues 18–89). The C-terminal domain (large domain A) is connected to the N-domain and contains a long α-helix (α2 or the toxin backbone; residues 125-141) packed against fiveβ strands; residues 90–194) that form a β-grasp motif [ 18 , 19 , 20 ]. N-terminal domain of TSST-1 binds MHC-II, while C-terminal domainis implicated in binding to TCR-Vβ [ 10 , 16 , 18 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Human scFvs That Counteract Bioactivities of Staphylococcus aureus TSST-1

Rukkawattanakul

Sookrung

Seesuay

et al. 2017

Toxins

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Some Staphylococcus aureus isolates produced toxic shock syndrome toxin-1 (TSST-1) which is a pyrogenic toxin superantigen (PTSAg). The toxin activates a large fraction of peripheral blood T lymphocytes causing the cells to proliferate and release massive amounts of pro-inflammatory cytokines leading to a life-threatening multisystem disorder: toxic shock syndrome (TSS). PTSAg-mediated-T cell stimulation circumvents the conventional antigenic peptide presentation to T cell receptor (TCR) by the antigen-presenting cell (APC). Instead, intact PTSAg binds directly to MHC-II molecule outside peptide binding cleft and simultaneously cross-links TCR-Vβ region. Currently, there is neither specific TSS treatment nor drug that directly inactivates TSST-1. In this study, human single chain antibodies (HuscFvs) that bound to and neutralized bioactivities of the TSST-1 were generated using phage display technology. Three E. coli clones transfected with TSST-1-bound phages fished-out from the human scFv library using recombinant TSST-1 as bait expressed TSST-1-bound-HuscFvs that inhibited the TSST-1-mediated T cell activation and pro-inflammatory cytokine gene expressions and productions.Computerized simulation, verified by mutations of the residues of HuscFv complementarity determining regions (CDRs),predicted to involve in target binding indicated that the HuscFvs formed interface contact with the toxin residues important for immunopathogenesis. The HuscFvs have high potential for future therapeutic application.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human scFvs That Counteract Bioactivities of Staphylococcus aureus TSST-1

Rukkawattanakul

Sookrung

Seesuay

et al. 2017

Toxins

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“…Our STRALCP system creates such a clustering automatically ( Figure 4 ). By this clustering the EAP structures: 1yn3-5 are grouped together (Cluster2) with four other protein structures: SET1 (PDB: 1v1p) ( 21 ), SET3 (PDB: 1m4v) ( 22 ), and TSST1 (PDB: 1aw7, 2tss) ( 23 , 24 ). Additional tests showed that if we had introduced more strict structure similarity requirements [e.g.…”

Section: Resultsmentioning

confidence: 99%

STRALCP structure alignment-based clustering of proteins

Zemła

Geisbrecht

Smith

et al. 2007

Nucleic Acids Research

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Protein structural annotation and classification is an important and challenging problem in bioinformatics. Research towards analysis of sequence–structure correspondences is critical for better understanding of a protein's structure, function, and its interaction with other molecules. Clustering of protein domains based on their structural similarities provides valuable information for protein classification schemes. In this article, we attempt to determine whether structure information alone is sufficient to adequately classify protein structures. We present an algorithm that identifies regions of structural similarity within a given set of protein structures, and uses those regions for clustering. In our approach, called STRALCP (STRucture ALignment-based Clustering of Proteins), we generate detailed information about global and local similarities between pairs of protein structures, identify fragments (spans) that are structurally conserved among proteins, and use these spans to group the structures accordingly. We also provide a web server at http://as2ts.llnl.gov/AS2TS/STRALCP/ for selecting protein structures, calculating structurally conserved regions and performing automated clustering.

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Overview of Protein Structural and Functional Folds

2004

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This overview provides an illustrated, comprehensive survey of some commonly observed protein-fold families and structural motifs, chosen for their functional significance. It opens with descriptions and definitions of the various elements of protein structure and associated terminology. Following is an introduction into web-based structural bioinformatics that includes surveys of interactive web servers for protein fold or domain annotation, protein-structure databases, protein-structure-classification databases, structural alignments of proteins, and molecular graphics programs available for personal computers. The rest of the overview describes selected families of protein folds in terms of their secondary, tertiary, and quaternary structural arrangements, including ribbon-diagram examples, tables of representative structures with references, and brief explanations pointing out their respective biological and functional significance.

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Refined structures of three crystal forms of toxic shock syndrome toxin‐1 and of a tetramutant with reduced activity

Cited by 26 publications

References 57 publications

Human scFvs That Counteract Bioactivities of Staphylococcus aureus TSST-1

Human scFvs That Counteract Bioactivities of Staphylococcus aureus TSST-1

STRALCP structure alignment-based clustering of proteins

Overview of Protein Structural and Functional Folds

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