scholarly journals Structural Characterization of Competence-Stimulating Peptide Analogues Reveals Key Features for ComD1 and ComD2 Receptor Binding in Streptococcus pneumoniae

Biochemistry ◽  
2018 ◽  
Vol 57 (36) ◽  
pp. 5359-5369 ◽  
Author(s):  
Yifang Yang ◽  
Gabriel Cornilescu ◽  
Yftah Tal-Gan
Keyword(s):  
Streptococcus Pneumoniae ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Key Features ◽  
Peptide Analogues

scholarly journals Isolation and structural characterization of insulin and glucagon from the holocephalan species Callorhynchus milii (elephantfish)

1989 ◽  
Vol 263 (1) ◽  
pp. 261-266 ◽  
Author(s):  
B C Berks ◽  
C J Marshall ◽  
A Carne ◽  
S M Galloway ◽  
J F Cutfield
Keyword(s):  
Gas Phase ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Sequence Similarity ◽  
Cartilaginous Fish ◽  
Proteolytic Processing ◽  
Reverse Phase ◽  
High Sequence Similarity ◽  
Processing Mechanisms

Both insulin and glucagon from the pancreas of the holocephalan cartilaginous fish Callorhynchus milii (elephantfish) have been isolated and purified. Two reverse-phase h.p.l.c. steps enabled recovery of sufficient material for gas-phase sequencing of the intact chains as well as peptide digestion products. The elephantfish insulin sequence shows 14 differences from pig insulin, including two unusual substitutions, Val-A14 and Gln-B30, though none of these is thought likely to influence receptor binding significantly. The insulin B-chain contains 31 residues, one more than mammalian insulins, but markedly less than that of the closely related ratfish with which it otherwise exhibits high sequence similarity. Elephantfish and pig glucagons differ at only four positions, but there are six changes from the ratfish glucagon-36 (normal glucagon contains 29 residues) sequence. It is apparent that different prohormone proteolytic processing mechanisms operate in the two holocephalan species.

scholarly journals Structural Characterization of N‐Linked Glycans in the Receptor Binding Domain of the SARS‐CoV‐2 Spike Protein and their Interactions with Human Lectins

2020 ◽  
Vol 132 (52) ◽  
pp. 23971-23979 ◽  
Author(s):  
Maria Pia Lenza ◽  
Iker Oyenarte ◽  
Tammo Diercks ◽  
Jon Imanol Quintana ◽  
Ana Gimeno ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structural Characterization ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain

scholarly journals Structural Characterization of the Essential Cell Division Protein FtsE and Its Interaction with FtsX in Streptococcus pneumoniae

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Martin Alcorlo ◽  
Daniel Straume ◽  
Joe Lutkenhaus ◽  
Leiv Sigve Håvarstein ◽  
Juan A. Hermoso
Keyword(s):  
Cell Wall ◽  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Structural Characterization ◽  
Bound States ◽  
Structural Information ◽  
Structural Plasticity ◽  
Membrane Complex

ABSTRACT FtsEX is a membrane complex widely conserved across diverse bacterial genera and involved in critical processes such as recruitment of division proteins and in spatial and temporal regulation of muralytic activity during cell division or sporulation. FtsEX is a member of the ABC transporter superfamily. The component FtsX is an integral membrane protein, whereas FtsE is an ATPase and is required for the transmission of a conformational signal from the cytosol through the membrane to regulate the activity of cell wall hydrolases in the periplasm. Both proteins are essential in the major human respiratory pathogenic bacterium Streptococcus pneumoniae, and FtsX interacts with the modular peptidoglycan hydrolase PcsB at the septum. Here, we report high-resolution structures of pneumococcal FtsE bound to different nucleotides. Structural analysis revealed that FtsE contains all the conserved structural motifs associated with ATPase activity and afforded interpretation of the in vivo dimeric arrangement in both the ADP and ATP states. Interestingly, three specific FtsE regions with high structural plasticity were identified that shape the cavity in which the cytosolic region of FtsX would be inserted. The residues corresponding to the FtsX coupling helix, responsible for contacting FtsE, were identified and validated by in vivo mutagenesis studies showing that this interaction is essential for cell growth and proper morphology. IMPORTANCE Bacterial cell division is a central process that requires exquisite orchestration of both the cell wall biosynthetic and lytic machineries. The essential membrane complex FtsEX, widely conserved across bacteria, plays a central role by recruiting proteins to the divisome apparatus and by regulating periplasmic muralytic activity from the cytosol. FtsEX is a member of the type VII family of the ABC-superfamily, but instead of being a transporter, it couples the ATP hydrolysis catalyzed by FtsE to mechanically transduce a conformational signal that provokes the activation of peptidoglycan (PG) hydrolases. So far, no structural information is available for FtsE. Here, we provide the structural characterization of FtsE, confirming its ATPase nature and revealing regions with high structural plasticity which are key for FtsE binding to FtsX. The complementary binding region in FtsX has also been identified and validated in vivo. Our results provide evidence on how the difference between the ATP/ADP-bound states in FtsE would dramatically alter the interaction of FtsEX with the PG hydrolase PcsB in pneumococcal division.

scholarly journals Structural characterization of the essential cell division protein FtsE and its interaction with FtsX in Streptococcus pneumoniae

2020 ◽  
Author(s):  
Martin Alcorlo ◽  
Daniel Straume ◽  
Joe Lutkenhaus ◽  
Leiv Sigve Håvarstein ◽  
Juan A. Hermoso
Keyword(s):  
Cell Wall ◽  
Cell Division ◽  
Streptococcus Pneumoniae ◽  
Structural Characterization ◽  
Structural Information ◽  
Structural Plasticity ◽  
Central Process ◽  
Membrane Complex

ABSTRACTFtsEX is a membrane complex widely conserved across diverse bacterial genera and involved in critical processes such as recruitment of division proteins and in spatial and temporal regulation of muralytic activity during cell division or sporulation. FtsEX is a member of the ABC transporter superfamily, where FtsX is an integral membrane protein and FtsE is an ATPase, required for mechanotransmission of the signal from the cytosol through the membrane, to regulate the activity of cell-wall hydrolases in the periplasm. Both proteins are essential in the major human respiratory pathogenic bacterium, Streptococcus pneumoniae and interact with the modular peptidoglycan hydrolase PcsB at the septum. Here, we report the high-resolution structures of pneumococcal FtsE in complex with different nucleotides. Structural analysis reveals that FtsE contains all the conserved structural motifs associated with ATPase activity, and allowed interpretation of the in vivo dimeric arrangement in both ADP and ATP states. Interestingly, three specific FtsE regions were identified with high structural plasticity that shape the cavity in which the cytosolic region of FtsX would be inserted. The residues corresponding to the FtsX coupling helix, responsible for FtsE contact, were identified and validated by in vivo mutagenesis studies showing that this interaction is essential for cell growth and proper morphology.IMPORTANCEBacterial cell division is a central process that requires exquisite orchestration of both the cell wall biosynthetic and lytic machineries. The essential membrane complex FtsEX, widely conserved across bacteria, play a central role by recruiting proteins to the divisome apparatus and by regulating periplasmic muralytic activity from the cytosol. FtsEX is a member of the Type VII family of the ABC-superfamily but instead transporter, couple ATP hydrolysis by FtsE to mechanically transduce a conformational signal to activate PG hydrolases. So far, no structural information is available for FtsE. Here we provide the structural characterization of FtsE confirming its ATPase nature and revealing regions with high structural plasticity key for FtsX binding. The complementary region in FtsX has been also identified and validated in vivo. Our results provide evidences on how difference between ATP and ADP states in FtsE would dramatically alter FtsEX interaction with PG hydrolase PcsB in pneumococcal division.

Aminimides as Potential CNS Acting Agents. II Design, Synthesis, and Receptor Binding of 4′-Arylalkyl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

2008 ◽  
Vol 61 (1) ◽  
pp. 5 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
Juliette E. Neve ◽  
David A. Taylor
Keyword(s):  
Atypical Antipsychotic ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Marked Reduction ◽  
Second Generation ◽  
Functional Group ◽  
Design Synthesis ◽  
Biochemical Effects ◽  
Antipsychotic Activity

We report the synthesis of a series of second generation aminimide-based analogues of clozapine, investigating the length of the linker between the aminimide functional group and the introduced aryl moiety. The chemistry and structural characterization of this series of 4′-arylalkyl aminimide analogues of clozapine are described. Preliminary findings on the biochemical effects of linker length and type of aryl moiety on affinity for dopamine D4 and serotonin 5-HT2A receptors are discussed. All of the compounds showed a marked reduction in binding at the two receptors when compared with clozapine, thus showing a reduced potential for atypical antipsychotic activity.

Synthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogues of Clozapine. IV. The Effects of Aromaticity and Isosteric Replacement

2008 ◽  
Vol 61 (12) ◽  
pp. 930 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
Anna Podloucka ◽  
David A. Taylor
Keyword(s):  
Receptor Binding ◽  
Pharmacological Activity ◽  
Structural Characterization ◽  
Structural Model ◽  
Antipsychotic Agents ◽  
Pharmacological Effects ◽  
Aryl Group ◽  
Preliminary Results ◽  
Pharmacological Evaluation

We report the synthesis and preliminary pharmacological activity of a new series of tricyclic analogues of clozapine as potential antipsychotic agents for the treatment of schizophrenia. These compounds were designed based on a revised structural model, and investigate the length and nature of a designated linker (alkyl and alkyloxy) and the nature of the introduced aryl group (aromatic and heteroaromatic). The chemistry and structural characterization of this series of 4′-arylalkyl(oxy) analogues of clozapine are described. Preliminary results on the pharmacological effects of the selected linkers and introduced aryl groups on affinity for dopamine D4 and serotonin 5-HT2A receptors are discussed. Psychosis-related animal behavioural data for promising compounds identified from the receptor binding screen are also presented.

scholarly journals Structural characterization of pneumococcal surface antigen A (PsaA) of Streptococcus pneumoniae

2013 ◽  
Author(s):  
Izabella Silva ◽  
Ana Ano Bom ◽  
Ana Argondizzo ◽  
Ariane Larentis ◽  
Marco Medeiros ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Surface Antigen ◽  
Structural Characterization ◽  
Antigen A
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