Abstract:
:Beta-lactams exert their antibiotic action through their inhibition of bacterial DD-peptidases (penicillin-binding proteins). Bacteria, in general, carry several such enzymes localized on the outside of their cell membrane to catalyze the final step in cell wall (peptidoglycan) synthesis. They have been classified into two major groups, one of high molecular weight, the other of low. Members of the former group act as transpeptidases in vivo, and their inhibition by beta-lactams leads to cessation of bacterial growth. The latter group consists of DD-carboxypeptidases, and their inhibition by beta-lactams is generally not fatal to bacteria. We have previously shown that representatives of the former group are ineffective at catalyzing the hydrolysis/aminolysis of peptidoglycan-mimetic peptides in vitro [Anderson et al. (2003) Biochem. J. 373, 949-955]. The theme of these experiments is expanded in the present paper where we describe the synthesis of a series of beta-lactams (penicillins and cephalosporins) containing peptidoglycan-mimetic side chains and the kinetics of their inhibition of a panel of penicillin-binding proteins spanning the major classes (Escherichia coli PBP 2 and PBP 5, Streptococcus pneumoniae PBP 1b, PBP 2x and PBP 3, the Actinomadura R39 DD-peptidase, and the Streptomyces R61 DD-peptidase). The results of these experiments mirror and expand the previous results with peptides. Neither peptides nor beta-lactams with appropriate peptidoglycan-mimetic side chains react with the solubilized constructs of membrane-bound penicillin binding proteins (the first five enzymes above) at rates exceeding those of generic analogues. Such peptides and beta-lactams do react at greatly enhanced rates with certain soluble low molecular weight enzymes (R61 and R39 DD-peptidases). The former result is unexpected and interesting. Why do the majority of penicillin-binding proteins not recognize elements of local peptidoglycan structure? Possible answers are discussed. That this question needs to be asked casts fascinating shadows on current studies of penicillin-binding proteins for new drug design.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Josephine HR,Charlier P,Davies C,Nicholas RA,Pratt RFdoi
10.1021/bi061804fsubject
Has Abstractpub_date
2006-12-26 00:00:00pages
15873-83issue
51eissn
0006-2960issn
1520-4995journal_volume
45pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The dynamic behavior of the rRNA A-site plays an important functional role. We have employed femtosecond time-resolved spectroscopy to investigate the nature of the conformational dynamics. In the drug-free state, the A-site samples multiple distinct conformations. Drug binding shifts the population distribution in a ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400053s
更新日期:2013-03-12 00:00:00
abstract::Three mutants, Asp55-Gly, Tyr306-->Phe, and Asp309-->Asn, of Aspergillus awamori glucoamylase (identical to Aspergillus niger glucoamylase) were constructed to elucidate the roles of two conserved regions within fungal glucoamylases. Kinetic studies indicate that both of these regions are closely associated with activ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00055a017
更新日期:1993-02-02 00:00:00
abstract::The EcoRV restriction endonuclease cleaves DNA at its recognition sequence more readily with Mg2+ as the cofactor than with Mn2+ but, at noncognate sequences that differ from the EcoRV site by one base pair, Mn2+ gives higher rates than Mg2+. A mutant of EcoRV, in which an isoleucine near the active site was replaced ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9523926
更新日期:1996-02-13 00:00:00
abstract::A protocol for complete isotopic labeling of iso-1-cytochrome c from the eukaryote Saccharomyces cerevisiae is reported. Assignments are reported for the vast majority of the 15N amide resonances in both oxidized and reduced states. 15N heteronuclear relaxation experiments were collected to study the picosecond-nanose...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9827417
更新日期:1999-04-06 00:00:00
abstract::The unfolding of human plasma alpha 1-acid glycoprotein (AGP) induced by heat or guanidine hydrochloride was studied under equilibrium conditions. In thermal unfolding, an intermediate state was detected by the appearance of unusual positive difference absorption bands in the 287-295-nm region, which occurred at lower...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00489a026
更新日期:1990-09-18 00:00:00
abstract::The interaction of lipoprotein lipase (LpL) and a nonhydrolyzable phosphatidylcholine, 1,2-ditetradecyl-rac-glycero-3-phosphocholine (C14-ether-PC), has been studied by several physical methods. Analysis of the circular dichroic spectrum of LpL gave the following fractional conformation: 35% alpha-helix, 30% beta-plea...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00352a020
更新日期:1986-02-25 00:00:00
abstract::"Charged-to alanine" scanning mutagenesis of the catalytic subunit of the Saccharomyces cerevisiae cAMP-dependent protein kinase (C1) identified three glutamate residues, E171, E214, and E274, that are involved in the recognition of a peptide substrate, kemptide (Leu1Arg2Arg3Ala4Ser5Leu6Gly7). These glutamate residues...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00236a001
更新日期:1991-06-04 00:00:00
abstract::Doxorubicin (DOX) is a chemotherapeutic that is used in the treatment of a wide variety of cancers. However, it causes cardiotoxicity partly because of the formation of reactive oxygen species. CYP2J2 is a human cytochrome P450 that is strongly expressed in cardiomyocytes. It converts arachidonic acid (AA) into four d...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b01025
更新日期:2017-12-26 00:00:00
abstract::Despite much work, subcellular neurons of Caenorhabditis elegans have not been studied at nanometer resolution with millisecond time resolution. Nor has there been an effective way to immobilize C. elegans. Here we show that, without using anesthetic or paralyzing agents, fluorescence imaging with one-nanometer accura...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8023477
更新日期:2009-06-09 00:00:00
abstract::Two site-directed mutant enzymes of the class A beta-lactamase from Staphylococcus aureus PC1 were produced with the goal of blocking the site that in the native enzyme is occupied by the proposed hydrolytic water molecule. The crystal structures of these two mutant enzymes, N170Q and N170M, have been determined and r...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi962242a
更新日期:1996-12-24 00:00:00
abstract::The chemoreceptors of Escherichia coli are homodimeric membrane proteins that cluster in patches near the cell poles. They convert environmental stimuli into intracellular signals that control flagellar rotation. The functional domains of a receptor are physically separated by the cell membrane. Chemoeffectors bind to...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi048969d
更新日期:2005-02-01 00:00:00
abstract::The Cry1Ab toxin produced by Bacillus thuringiensis (Bt) exerts insecticidal action upon binding to BT-R1, a cadherin receptor localized in the midgut epithelium of the tobacco hornworm Manduca sexta [Dorsch, J. A., Candas, M., Griko, N. B., Maaty, W. S., Midboe, E. G., Vadlamudi, R. K., and Bulla, L. A., Jr. (2002) C...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700769s
更新日期:2007-09-04 00:00:00
abstract::We have visualized by freeze-etch electron microscopy the macromolecular complexes of complement, C5b-8 and C5b-9, respectively, assembled on synthetic phospholipid bilayers. These complexes were formed sequentially by using purified human complement components C5b-6 followed by C7, C8, and C9. Complexes of C5b-8 were...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00428a019
更新日期:1989-01-24 00:00:00
abstract::Sumoylation, the process by which the ubiquitin-related SUMO protein is covalently attached to lysine side chains in other proteins, is involved in numerous processes in the eukaryotic cell, including transcriptional repression. In this study, we identify Gcn5, the histone-modifying subunit of the transcriptional regu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051624q
更新日期:2006-01-24 00:00:00
abstract::The presumed role of an overactive protein arginine deiminase 4 (PAD4) in the pathophysiology of rheumatoid arthritis (RA) suggests that PAD4 inhibitors could be used to treat an underlying cause of RA, potentially offering a mechanism to stop further disease progression. Thus, the development of such inhibitors is of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700095s
更新日期:2007-06-05 00:00:00
abstract::Amyloid-beta (Abeta) peptide deposition as fibrillar senile plaques is a key element in the pathology of Alzheimer's disease. Here we present a high-resolution structure of an Abeta amyloid fibril using magnetically aligned preparations of a central Abeta domain which forms representative amyloid fibrils. Diffraction ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000637v
更新日期:2000-10-31 00:00:00
abstract::Human melanin-concentrating hormone (hMCH) and many of its analogues are potent but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of these receptors, selective antagonists are needed. In this study, analogues of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0200514
更新日期:2002-05-21 00:00:00
abstract::The ability to undergo large-scale domain rearrangements is essential for the substrate-binding function of periplasmic binding proteins (PBPs), which are indispensable for nutrient uptake in Gram-negative bacteria. Crystal structures indicate that PBPs typically adopt either an "open" unliganded configuration or a "c...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi902045p
更新日期:2010-03-09 00:00:00
abstract::Protein electrochemistry in an ultra-thin-layer electrochemical cell suitable for UV/vis and IR spectroscopy has been used to characterize the vibrational modes of the primary electron donors of Rhodobacter sphaeroides and Rhodopseudomonas viridis reaction centers in their neutral and cation radical states (P and P+, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00068a007
更新日期:1993-05-04 00:00:00
abstract::Vibrational Raman spectroscopic experiments have been performed as a function of temperature on aqueous dispersions of synthetic DL-erythro-N-lignoceroylsphingosylphosphocholine [C(24):SPM], a racemic mixture of two highly asymmetric hydrocarbon chain length sphingomyelins. Raman spectral peak-height intensity ratios ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00343a036
更新日期:1985-10-22 00:00:00
abstract::The organization and interaction of chlorophylls (Chl) and the kinetics of the energy transfer in the core antenna of photosystem I (PSI) trimeric and monomeric complexes, isolated from Spirulina platensis with Triton X-100 have been studied by stationary and time-resolved fluorescence. At 295 K both complexes show an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970386z
更新日期:1997-11-11 00:00:00
abstract::The amino acid sequence of the sex steroid binding protein (SBP) from human plasma has been determined. The SBP subunit consists of a 373-residue polypeptide chain containing two disulfide bonds and three oligosaccharide chains. The sequence was solved primarily by analysis of peptides derived by cleavage at either ly...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00371a048
更新日期:1986-11-18 00:00:00
abstract::Stopped-flow total intensity and anisotropy experiments on single tryptophan containing mutants of yeast phosphoglycerate kinase (PGK) located in either the carboxy-terminal domain (W308 and W333), amino-terminal domain (W48 and W122), or "hinge" region (W194 and W399) were performed. The results obtained for single t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00042a028
更新日期:1995-10-24 00:00:00
abstract::Pulmonary surfactant protein D (SP-D), a member of the collectin group of innate immune proteins, plays important roles in lipopolysaccharide (LPS) recognition. We have previously shown that surfactant protein A (SP-A), a homologous collectin, interacts with Toll-like receptor (TLR) 2, resulting in alteration of TLR2-...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060176z
更新日期:2006-07-18 00:00:00
abstract::Treatment of ADP-glucose pyrophosphorylase (EC 2.7.7.27) from the cyanobacterium Anabaena PCC 7120 with phenylglyoxal in 50 mM Hepes, pH 8.0, at 25 degrees C resulted in a time- and concentration-dependent loss of enzyme activity. Phosphate, the inhibitor, protected the enzyme from inactivation most effectively, while...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9713355
更新日期:1997-10-21 00:00:00
abstract::It has been shown (Poole et al., 1991) that deletion of residues 44-49 from the sequence of staphylococcal nuclease (E43 SNase) results in an enzyme (E43 delta SNase) that is significantly more active than D43 SNase, an enzyme that differs from the wild-type enzyme by deletion of a single methylene group. In addition,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00229a006
更新日期:1991-04-16 00:00:00
abstract::Calmodulin and troponin C exhibit calcium-dependent binding of 1 mol/mol of dynorphin. The dissociation constants of the complexes, determined in 0.20 N KC1-1.0 mM CaCI2, pH 7.3, are 0.6 microM for calmodulin, 2.4 microM for rabbit fast skeletal muscle troponin C, and 9 microM for bovine heart troponin C. Experiments ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00306a016
更新日期:1984-05-22 00:00:00
abstract::Evidence of nonequilibrium local heating in transient spectra of LHCII, the main light-harvesting complex of plants, was studied by using various excitation intensities over a wide temperature range, from 10 K to room temperature. No obvious manifestation of local heating was found at room temperature, whereas at 10 K...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060048a
更新日期:2006-08-08 00:00:00
abstract::The denaturation of the heat shock protein DnaK induced by guanidine hydrochloride (Gdn-HCl) was investigated by circular dichroism, fluorescence, size-exclusion HPLC, and dynamic light scattering. DnaK unfolding takes place in two discrete steps. The midpoint (Cm) of the first transition (0.5 M) was shifted to higher...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00067a021
更新日期:1993-04-27 00:00:00
abstract::A crude in vitro system which initiates chloroplast DNA synthesis near the D-loop site mapped by electron microscopy [Wu, M., Lou, J. K., Chang, D. Y., Chang, C. H., & Nie, Z. Q. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 6761-6765] consists of soluble proteins and proteins extracted from purified thylakoid membrane. In...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00218a034
更新日期:1991-01-29 00:00:00