The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kurt L. Krause - One of the best experts on this subject based on the ideXlab platform.
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the crystal structure of alanine racemase from streptococcus pneumoniae a target for structure based drug design
BMC Microbiology, 2011Co-Authors: Hookang Im, Milya Davlieva, Ulrich Strych, Miriam L Sharpe, Kurt L. KrauseAbstract:Background Streptococcus pneumoniae is a globally important pathogen. The Gram-positive diplococcus is a leading cause of pneumonia, otitis media, bacteremia, and meningitis, and antibiotic resistant strains have become increasingly common over recent years.Alanine racemase is a ubiquitous enzyme among bacteria and provides the Essential Cell wall precursor, D-alanine. Since it is absent in humans, this enzyme is an attractive target for the development of drugs against S. pneumoniae and other bacterial pathogens.
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purification and preliminary crystallization of alanine racemase from streptococcus pneumoniae
BMC Microbiology, 2007Co-Authors: Ulrich Strych, Eileen L Murphy, Hookang Im, Kurt L. Krause, Milya Davlieva, Michael J. Benedik, Joseph P LongtinAbstract:Background Over the past fifteen years, antibiotic resistance in the Gram-positive opportunistic human pathogen Streptococcus pneumoniae has significantly increased. Clinical isolates from patients with community-acquired pneumonia or otitis media often display resistance to two or more antibiotics. Given the need for new therapeutics, we intend to investigate enzymes of Cell wall biosynthesis as novel drug targets. Alanine racemase, a ubiquitous enzyme among bacteria and absent in humans, provides the Essential Cell wall precursor, D-alanine, which forms part of the tetrapeptide crosslinking the peptidoglycan layer.
Hookang Im - One of the best experts on this subject based on the ideXlab platform.
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the crystal structure of alanine racemase from streptococcus pneumoniae a target for structure based drug design
BMC Microbiology, 2011Co-Authors: Hookang Im, Milya Davlieva, Ulrich Strych, Miriam L Sharpe, Kurt L. KrauseAbstract:Background Streptococcus pneumoniae is a globally important pathogen. The Gram-positive diplococcus is a leading cause of pneumonia, otitis media, bacteremia, and meningitis, and antibiotic resistant strains have become increasingly common over recent years.Alanine racemase is a ubiquitous enzyme among bacteria and provides the Essential Cell wall precursor, D-alanine. Since it is absent in humans, this enzyme is an attractive target for the development of drugs against S. pneumoniae and other bacterial pathogens.
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purification and preliminary crystallization of alanine racemase from streptococcus pneumoniae
BMC Microbiology, 2007Co-Authors: Ulrich Strych, Eileen L Murphy, Hookang Im, Kurt L. Krause, Milya Davlieva, Michael J. Benedik, Joseph P LongtinAbstract:Background Over the past fifteen years, antibiotic resistance in the Gram-positive opportunistic human pathogen Streptococcus pneumoniae has significantly increased. Clinical isolates from patients with community-acquired pneumonia or otitis media often display resistance to two or more antibiotics. Given the need for new therapeutics, we intend to investigate enzymes of Cell wall biosynthesis as novel drug targets. Alanine racemase, a ubiquitous enzyme among bacteria and absent in humans, provides the Essential Cell wall precursor, D-alanine, which forms part of the tetrapeptide crosslinking the peptidoglycan layer.
Waldemar Vollmer - One of the best experts on this subject based on the ideXlab platform.
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activities and regulation of peptidoglycan synthases
Philosophical Transactions of the Royal Society B, 2015Co-Authors: Alexander J F Egan, Jacob Biboy, Inge Vant L Veer, Eefjan Breukink, Waldemar VollmerAbstract:Peptidoglycan (PG) is an Essential component in the Cell wall of nearly all bacteria, forming a continuous, mesh-like structure, called the sacculus, around the cytoplasmic membrane to protect the Cell from bursting by its turgor. Although PG synthases, the penicillin-binding proteins (PBPs), have been studied for 70 years, useful in vitro assays for measuring their activities were established only recently, and these provided the first insights into the regulation of these enzymes. Here, we review the current knowledge on the glycosyltransferase and transpeptidase activities of PG synthases. We provide new data showing that the bifunctional PBP1A and PBP1B from Escherichia coli are active upon reconstitution into the membrane environment of proteoliposomes, and that these enzymes also exhibit DD-carboxypeptidase activity in certain conditions. Both novel features are relevant for their functioning within the Cell. We also review recent data on the impact of protein–protein interactions and other factors on the activities of PBPs. As an example, we demonstrate a synergistic effect of multiple protein–protein interactions on the glycosyltransferase activity of PBP1B, by its cognate lipoprotein activator LpoB and the Essential Cell division protein FtsN.
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glutamate 83 and arginine 85 of helix h3 bend are key residues for ftsz polymerization gtpase activity and Cellular viability of escherichia coli lateral mutations affect ftsz polymerization and e coli viability
BMC Microbiology, 2013Co-Authors: Jae Yen Shin, Waldemar Vollmer, Rosalba Lagos, Octavio MonasterioAbstract:Background FtsZ is an Essential Cell division protein, which localizes at the middle of the bacterial Cell to mediate cytokinesis. In vitro, FtsZ polymerizes and induces GTPase activity through longitudinal interactions to form the protofilaments, whilst lateral interactions result within formation of bundles. The interactions that participate in the protofilaments are similar to its eukaryotic homologue tubulin and are well characterized; however, lateral interactions between the inter protofilaments are less defined. FtsZ forms double protofilaments in vitro, though the key elements on the interface of the inter-protofilaments remain unclear as well as the structures involved in the lateral interactions in vivo and in vitro. In this study, we demonstrate that the highly conserved negative charge of glutamate 83 and the positive charge of arginine 85 located in the helix H3 bend of FtsZ are required for in vitro FtsZ lateral and longitudinal interactions, respectively and for in vivo Cell division.
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osmolality dependent relocation of penicillin binding protein pbp2 to the division site in caulobacter crescentus
Journal of Bacteriology, 2012Co-Authors: Jason Hocking, Waldemar Vollmer, Richa Priyadarshini, Constantin N Takacs, Teresa Costa, Natalie A Dye, Lucy Shapiro, Christine JacobswagnerAbstract:The synthesis of the peptidoglycan Cell wall is carefully regulated in time and space. In nature, this Essential process occurs in Cells that live in fluctuating environments. Here we show that the spatial distributions of specific Cell wall proteins in Caulobacter crescentus are sensitive to small external osmotic upshifts. The penicillin-binding protein PBP2, which is commonly branded as an Essential Cell elongation-specific transpeptidase, switches its localization from a dispersed, patchy pattern to an accumulation at the FtsZ ring location in response to osmotic upshifts as low as 40 mosmol/kg. This osmolality-dependent relocation to the division apparatus is initiated within less than a minute, while restoration to the patchy localization pattern is dependent on Cell growth and takes 1 to 2 generations. Cell wall morphogenetic protein RodA and penicillin-binding protein PBP1a also change their spatial distribution by accumulating at the division site in response to external osmotic upshifts. Consistent with its ecological distribution, C. crescentus displays a narrow range of osmotolerance, with an upper limit of 225 mosmol/kg in minimal medium. Collectively, our findings reveal an unsuspected level of environmental regulation of Cell wall protein behavior that is likely linked to an ecological adaptation.
Ulrich Strych - One of the best experts on this subject based on the ideXlab platform.
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the crystal structure of alanine racemase from streptococcus pneumoniae a target for structure based drug design
BMC Microbiology, 2011Co-Authors: Hookang Im, Milya Davlieva, Ulrich Strych, Miriam L Sharpe, Kurt L. KrauseAbstract:Background Streptococcus pneumoniae is a globally important pathogen. The Gram-positive diplococcus is a leading cause of pneumonia, otitis media, bacteremia, and meningitis, and antibiotic resistant strains have become increasingly common over recent years.Alanine racemase is a ubiquitous enzyme among bacteria and provides the Essential Cell wall precursor, D-alanine. Since it is absent in humans, this enzyme is an attractive target for the development of drugs against S. pneumoniae and other bacterial pathogens.
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purification and preliminary crystallization of alanine racemase from streptococcus pneumoniae
BMC Microbiology, 2007Co-Authors: Ulrich Strych, Eileen L Murphy, Hookang Im, Kurt L. Krause, Milya Davlieva, Michael J. Benedik, Joseph P LongtinAbstract:Background Over the past fifteen years, antibiotic resistance in the Gram-positive opportunistic human pathogen Streptococcus pneumoniae has significantly increased. Clinical isolates from patients with community-acquired pneumonia or otitis media often display resistance to two or more antibiotics. Given the need for new therapeutics, we intend to investigate enzymes of Cell wall biosynthesis as novel drug targets. Alanine racemase, a ubiquitous enzyme among bacteria and absent in humans, provides the Essential Cell wall precursor, D-alanine, which forms part of the tetrapeptide crosslinking the peptidoglycan layer.
Jeanphilippe Brouland - One of the best experts on this subject based on the ideXlab platform.
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altered endoplasmic reticulum calcium pump expression during breast tumorigenesis
Breast Cancer: Basic and Clinical Research, 2011Co-Authors: Bela Papp, Jeanphilippe BroulandAbstract:Endoplasmic reticulum calcium homeostasis is involved in several Essential Cell functions including Cell proliferation, protein synthesis, stress responses or secretion. Calcium uptake into the endoplasmic reticulum is performed by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). In order to study endoplasmic reticulum calcium homeostasis in situ in mammary tissue, in this work SERCA3 expression was investigated in normal breast and in its benign and malignant lesions in function of the Cell type, degree of malignancy, and histological and molecular parameters of the tumors. Our data indicate, that although normal breast acinar epithelial Cells express SERCA3 abundantly, its expression is strongly decreased already in very early non-malignant epithelial lesions such as adenosis, and remains low in lobular carcinomas. Whereas normal duct epithelium expresses significant amounts of SERCA3, its expression is decreased in several benign ductal lesions, as well as in ductal adenocarcinoma. The loss of SERCA3 expression is correlated with Elston-Ellis grade, negative hormone receptor expression or triple negative status in ductal carcinomas. The concordance between decreased SERCA3 expression and several histological, as well as molecular markers of ductal carcinogenesis indicates that endoplasmic reticulum calcium homeostasis is remodeled during tumorigenesis in the breast epithelium.