Chemistry & biology

Publisher: Elsevier

Journal description

Current impact factor: 6.59

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 6.586
2012 Impact Factor 6.157
2011 Impact Factor 5.829
2010 Impact Factor 5.838
2009 Impact Factor 6.523
2008 Impact Factor 5.603
2007 Impact Factor 5.718
2006 Impact Factor 6.677
2005 Impact Factor 6.138
2004 Impact Factor 5.725
2003 Impact Factor 6.129
2002 Impact Factor 6.109
2001 Impact Factor 5.987
2000 Impact Factor 5.717
1999 Impact Factor 6.242
1998 Impact Factor 6.157
1997 Impact Factor 5.796

Impact factor over time

Impact factor
Year

Additional details

5-year impact 6.37
Cited half-life 6.10
Immediacy index 1.46
Eigenfactor 0.03
Article influence 2.54
Other titles Chemistry & biology (Online), Chemistry & biology, Chemistry and biology
ISSN 1879-1301
OCLC 37104323
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Elsevier

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On authors personal or authors institutions server
    • Published source must be acknowledged
    • Must link to journal home page
    • Publisher's version/PDF cannot be used
    • 'Elsevier (Cell Press)' is an imprint of 'Elsevier'
  • Classification
    ​ blue

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pseudomonas aeruginosa uses the alkylquinolones PQS (2-heptyl-3-hydroxy-4(1H)-quinolone) and HHQ (2-heptyl-4(1H)-quinolone) as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. The biosynthesis of HHQ is generally accepted to require the pqsABCD gene products. We now reconstitute the biosynthetic pathway in vitro, and demonstrate that in addition to PqsABCD, PqsE has a role in HHQ synthesis. PqsE acts as thioesterase, hydrolyzing the biosynthetic intermediate 2-aminobenzoylacetyl-coenzyme A to form 2-aminobenzoylacetate, the precursor of HHQ and 2-aminoacetophenone. The role of PqsE can be taken over to some extent by the broad-specificity thioesterase TesB, explaining why the pqsE deletion mutant of P. aeruginosa still synthesizes HHQ. Interestingly, the pqsE mutant produces increased levels of 2,4-dihydroxyquinoline, resulting from intramolecular cyclization of 2-aminobenzoylacetyl-coenzyme A. Overall, our data suggest that PqsE promotes the efficiency of alkylquinolone signal molecule biosynthesis in P. aeruginosa and balances the levels of secondary metabolites deriving from the alkylquinolone biosynthetic pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 05/2015; DOI:10.1016/j.chembiol.2015.04.012
  • [Show abstract] [Hide abstract]
    ABSTRACT: Proteases usually cleave peptides, but under some conditions, they can ligate them. Seeds of the common sunflower contain the 14-residue, backbone-macrocyclic peptide sunflower trypsin inhibitor 1 (SFTI-1) whose maturation from its precursor has a genetic requirement for asparaginyl endopeptidase (AEP). To provide more direct evidence, we developed an in situ assay and used (18)O-water to demonstrate that SFTI-1 is excised and simultaneously macrocyclized from its linear precursor. The reaction is inefficient in situ, but a newfound breakdown pathway can mask this inefficiency by reducing the internal disulfide bridge of any acyclic-SFTI to thiols before degrading it. To confirm AEP can directly perform the excision/ligation, we produced several recombinant plant AEPs in E. coli, and one from jack bean could catalyze both a typical cleavage reaction and cleavage-dependent, intramolecular transpeptidation to create SFTI-1. We propose that the evolution of ligating endoproteases enables plants like sunflower and jack bean to stabilize bioactive peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 05/2015; DOI:10.1016/j.chembiol.2015.04.010
  • [Show abstract] [Hide abstract]
    ABSTRACT: Understanding of protein complex assembly and the effect of ligand binding on their native topologies is integral to discerning how alterations in their architecture can affect function. Probing the disassembly pathway may offer insight into the mechanisms through which various subunits self-assemble into complexes. Here, a gas-phase dissociation method, surface-induced dissociation (SID) coupled with ion mobility (IM), was utilized to determine whether disassembly pathways are consistent with the assembly of three homotetramers and to probe the effects of ligand binding on conformational flexibility and tetramer stability. The results indicate that the smaller interface in the complex is initially cleaved upon dissociation, conserving the larger interface, and suggest that assembly of a D2 homotetramer from its constituent monomers occurs via a C2 dimer intermediate. In addition, we demonstrate that ligand-mediated changes in tetramer SID dissociation behavior are dependent on where and how the ligand binds. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; DOI:10.1016/j.chembiol.2015.03.019
  • [Show abstract] [Hide abstract]
    ABSTRACT: Secondary metabolite biosynthesis in microorganisms responds to discrete chemical and biological stimuli; however, untargeted identification of these responses presents a significant challenge. Herein we apply multiplexed stimuli to Streptomyces coelicolor and collect the resulting response metabolomes via ion mobility-mass spectrometric analysis. Self-organizing map (SOM) analytics adapted for metabolomic data demonstrate efficient characterization of the subsets of primary and secondary metabolites that respond similarly across stimuli. Over 60% of all metabolic features inventoried from responses are either not observed under control conditions or produced at greater than 2-fold increase in abundance in response to at least one of the multiplexing conditions, reflecting how metabolites encode phenotypic changes in an organism responding to multiplexed challenges. Using abundance as an additional filter, each of 16 known S. coelicolor secondary metabolites is prioritized via SOM and observed at increased levels (1.2- to 22-fold compared with unperturbed) in response to one or more challenge conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; DOI:10.1016/j.chembiol.2015.03.020
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although small molecules shed from pathogens are widely used to diagnose infection, such tests have not been widely implemented for tuberculosis. Here we show that the recently identified compound, 1-tuberculosinyladenosine (1-TbAd), accumulates to comprise >1% of all Mycobacterium tuberculosis lipid. In vitro and in vivo, two isomers of TbAd were detected that might serve as infection markers. Using mass spectrometry and nuclear magnetic resonance, we established the structure of the previously unknown molecule, N(6)-tuberculosinyladenosine (N(6)-TbAd). Its biosynthesis involves enzymatic production of 1-TbAd by Rv3378c followed by conversion to N(6)-TbAd via the Dimroth rearrangement. Intact biosynthetic genes are observed only within M. tuberculosis complex bacteria, and TbAd was not detected among other medically important pathogens, environmental bacteria, and vaccine strains. With no substantially similar known molecules in nature, the discovery and in vivo detection of two abundant terpene nucleosides support their development as specific diagnostic markers of tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):516-526. DOI:10.1016/j.chembiol.2015.03.015
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this issue, Young, Moody, and colleagues report the discovery of an isomer of the Mycobacterium tuberculosis (Mtb) virulence factor 1-tuberculosinyl adenosine, N(6)-tuberculosinyl adenosine, in mice infected with tuberculosis. These Mtb-derived terpene compounds may serve as sensitive and specific biomarkers of infection. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):437-438. DOI:10.1016/j.chembiol.2015.04.004
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rising antibiotic resistance means that alternative antibacterial strategies are sorely needed. In this issue, Zhu et al. (2015) report the use of a Caenorhabditis elegans model to validate the Pseudomonas aeruginosa virulence factor LasB as a potential therapeutic target and to identify a LasB inhibitor with in vivo efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):436-437. DOI:10.1016/j.chembiol.2015.04.005
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coenzyme A (CoA) is an ubiquitous and essential cofactor, synthesized from the precursor pantothenate. Vitamin biosynthetic pathways are normally tightly regulated, including the pathway from pantothenate to CoA. However, no regulation of pantothenate biosynthesis has been identified. We have recently described an additional component in the pantothenate biosynthetic pathway, PanZ, which promotes the activation of the zymogen, PanD, to form aspartate α-decarboxylase (ADC) in a CoA-dependent manner. Here we report the structure of PanZ in complex with PanD, which reveals the structural basis for the CoA dependence of this interaction and activation. In addition, we show that PanZ acts as a CoA-dependent inhibitor of ADC catalysis. This inhibitory effect can effectively regulate the biosynthetic pathway to pantothenate, and thereby also regulate CoA biosynthesis. This represents a previously unobserved mode of metabolic regulation whereby a cofactor-utilizing protein negatively regulates the biosynthesis of the same cofactor. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Chemistry & biology 04/2015; 22(4):492-503. DOI:10.1016/j.chembiol.2015.03.017
  • [Show abstract] [Hide abstract]
    ABSTRACT: The inflammatory response is a critical component of the immune system that is activated by stimuli such as cytokines, foreign DNA, RNA, or other harmful substances. Krukenberg et al. (2015) identify poly(ADP-ribose) as a new signaling molecule that activates inflammation, thus providing yet another mechanism by which PARPs are involved in cellular stress responses. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):432-433. DOI:10.1016/j.chembiol.2015.04.006
  • [Show abstract] [Hide abstract]
    ABSTRACT: Olson et al. (2015) propose that some hydroxamic acid-based small molecules, already in clinical use as histone deacetylase inhibitors, may protect against oxidative stress through a direct chemical reaction of dismutation of hydrogen peroxide into water. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):431-432. DOI:10.1016/j.chembiol.2015.04.003
  • [Show abstract] [Hide abstract]
    ABSTRACT: Understanding how compound penetration occurs across the complex cell walls of Gram-negative bacteria is one of the greatest challenges in discovering new drugs to treat the infections they cause. A combination of next-generation transposon sequencing, computational metadynamics simulations (CMDS), and medicinal chemistry was used to define genetic and structural elements involved in facilitated carbapenem entry into Pseudomonas aeruginosa. Here we show for the first time that these compounds are taken up not only by the major outer membrane channel OccD1 (also called OprD or PA0958) but also by a closely related channel OccD3 (OpdP or PA4501). Transport-mediating molecular interactions predicted by CMDS for these channels were first confirmed genetically, then used to guide the design of carbapenem analogs with altered uptake properties. These results bring us closer to the rational design of channel transmissibility and may ultimately lead to improved permeability of compounds across bacterial outer membranes. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):535-547. DOI:10.1016/j.chembiol.2015.03.018
  • [Show abstract] [Hide abstract]
    ABSTRACT: In less than two decades, activity-based protein profiling (ABPP) has expanded to become the de facto tool for the study of small molecule-protein interactions in a proteomic environment. In this issue, Na et al. (2015) present another ABPP method, which they called reactive probe-based chemical proteomics, to study host-pathogen interaction and subsequently identify the protein PheA as a potential key effector during the pathogen infection process. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):434-435. DOI:10.1016/j.chembiol.2015.04.002
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; 22(4):527-534. DOI:10.1016/j.chembiol.2015.03.016
  • [Show abstract] [Hide abstract]
    ABSTRACT: The emergence of antibiotic resistance places a sense of urgency on the development of alternative antibacterial strategies, of which targeting virulence factors has been regarded as a "second generation" antibiotic approach. In the case of Pseudomonas aeruginosa infections, a proteolytic virulence factor, LasB, is one such target. Unfortunately, we and others have not been successful in translating in vitro potency of LasB inhibitors to in vivo efficacy in an animal model. To overcome this obstacle, we now integrate in silico and in vitro identification of the mercaptoacetamide motif as an effective class of LasB inhibitors with full in vivo characterization of mercaptoacetamide prodrugs using Caenorhabditis elegans. We show that one of our mercaptoacetamide prodrugs has a good selectivity profile and high in vivo efficacy, and confirm that LasB is a promising target for the treatment of bacterial infections. In addition, our work highlights that the C. elegans infection model is a user-friendly and cost-effective translational tool for the development of anti-virulence compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Chemistry & biology 04/2015; DOI:10.1016/j.chembiol.2015.03.012