Abstract：
:The increased incidence of bacterial resistance to available antibiotics represents a major global health problem and highlights the need for novel anti-infective therapies. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. AMPs are versatile, have almost unlimited sequence space, and can be tuned for broad-spectrum or specific activity against microorganisms. However, several obstacles remain to be overcome in order to develop AMPs for medical use, such as toxicity, stability, and bacterial resistance. We lack standard experimental procedures for quantifying AMP activity and do not yet have a clear picture of the mechanisms of action of AMPs. The rational design of AMPs can help solve these issues and enable their use as new antimicrobials. Here we provide an overview of the main physicochemical features that can be engineered to achieve enhanced bioactivity and describe current strategies being used to design AMPs.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Torres MDT,Sothiselvam S,Lu TK,de la Fuente-Nunez Cdoi
10.1016/j.jmb.2018.12.015subject
Has Abstractpub_date
2019-08-23 00:00:00pages
3547-3567issue
18eissn
0022-2836issn
1089-8638pii
S0022-2836(18)31289-0journal_volume
431pub_type
杂志文章,评审abstract：:The crystal structures of three vancomycin complexes with two vancomycin-sensitive cell-wall precursor analogs (diacetyl-Lys-D-Ala-D-Ala and acetyl-D-Ala-D-Ala) and a vancomycin-resistant cell-wall precursor analog (diacetyl-Lys-D-Ala-D-lactate) were determined at atomic resolutions of 1.80 A, 1.07 A, and 0.93 A, resp...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.10.026
更新日期：2009-02-06 00:00:00
abstract：:Elastomeric proteins are molecular springs found not only in a variety of biological machines and tissues, but also in biomaterials of superb mechanical properties. Regulating the mechanical stability of elastomeric proteins is not only important for a range of biological processes, but also critical for the use of en...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.03.046
更新日期：2008-05-16 00:00:00
abstract：:As part of an overall effort to map the energetic landscape of the base excision repair pathway, we report the first thermodynamic characterization of repair enzyme binding to lesion-containing duplexes. Isothermal titration calorimetry (ITC) in conjunction with spectroscopic measurements and protease protection assay...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(03)00365-6
更新日期：2003-05-16 00:00:00
abstract：:Protein domains represent the basic evolutionary units that form proteins. Domain duplication and shuffling by recombination are probably the most important forces driving protein evolution and hence the complexity of the proteome. While the duplication of whole genes as well as domain-encoding exons increases the abu...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.11.050
更新日期：2005-02-11 00:00:00
abstract：:The evolution of new or improved enzyme specificities in prokaryotes has been proposed to involve gene duplication, followed by silencing of one of the duplicates at the transcriptional or translational level. Such "silent gene intermediates" are distinct from "cryptic" genes, which are proposed to have a different ro...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(86)90358-x
更新日期：1986-11-20 00:00:00
abstract：:Lipoyl-lysine swinging arms are crucial to the reactions catalysed by the 2-oxo acid dehydrogenase multienzyme complexes. A gene encoding a putative lipoate protein ligase (LplA) of Thermoplasma acidophilum was cloned and expressed in Escherichia coli. The recombinant protein, a monomer of molecular mass 29 kDa, was c...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.11.057
更新日期：2006-02-24 00:00:00
abstract：:The cytoplasmic surface topography of purple membranes imaged by the atomic force microscope depends mainly on the force applied to the stylus. Imaged at forces of 300 pN, individual bacteriorhodopsin molecules reveal two domains. The resulting donut-shaped trimers reversibly transform into structures exhibiting three...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1995.0292
更新日期：1995-06-02 00:00:00
abstract：:The periplasmic domain of the aspartate chemotaxis receptor from Salmonella typhimurium has been crystallized in the presence and absence of bound aspartate. Both crystal forms were grown by precipitation with lithium sulfate and diffract to 1.8 A resolution. The aspartate receptor structure is believed to be prototyp...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(91)80198-4
更新日期：1991-09-05 00:00:00
abstract：:Neurodegenerative disorders associated with protein misfolding are fatal diseases that are caused by fibrillation of endogenous proteins such as α-synuclein (α-syn) in Parkinson's disease (PD) or amyloid-β in Alzheimer's disease. Fibrils of α-syn are a major pathological hallmark of PD and certain aggregation intermed...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2015.01.020
更新日期：2015-03-27 00:00:00
abstract：:Lysyl and prolyl hydroxylations are well-known post-translational modifications to animal and plant proteins with extracellular roles. More recent work has indicated that the hydroxylation of intracellular animal proteins may be common. JMJD6 catalyses the iron- and 2-oxoglutarate-dependent hydroxylation of lysyl resi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：
更新日期：2010-08-13 00:00:00
abstract：:The E. coli RecBCD enzyme facilitates the loading of RecA onto single-stranded DNA produced by the combined helicase/nuclease activity of RecBCD. The nuclease domain of RecB protein, RecB(nuc), has been previously shown to bind RecA. Surprisingly, RecB(nuc) also binds to phage and eukaryotic homologs of RecA, leading ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.06.042
更新日期：2009-08-14 00:00:00
abstract：:The human kinetochore is a highly complex macromolecular structure that connects chromosomes to spindle microtubules (MTs) in order to facilitate accurate chromosome segregation. Centromere-associated protein E (CENP-E), a member of the kinesin superfamily, is an essential component of the kinetochore, since it is req...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.05.053
更新日期：2004-07-23 00:00:00
abstract：:The structure of the complex between a recombinant single-chain Fv construct of antibody NC10 with a five-residue peptide linker between VH and VL (termed scFv(5)), and its antigen, tetrameric neuraminidase from influenza virus (NA), has been determined and refined at 2.5 A resolution. The antibody-antigen binding int...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.1794
更新日期：1998-06-19 00:00:00
abstract：:Microglia, the resident macrophages of the central nervous system, critically influence neural function during development and in adulthood. Microglia are also profoundly sensitive to insults to the brain to which they respond with process of activation that includes spectrum of changes in morphology, function, and ge...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2019.01.016
更新日期：2019-04-19 00:00:00
abstract：:Eukaryotic aminoacyl-tRNA synthetases are usually organized into high-molecular-weight complexes, the structure and function of which are poorly understood. We have previously described a yeast complex containing two aminoacyl-tRNA synthetases, methionyl-tRNA synthetase and glutamyl-tRNA synthetase, and one noncatalyt...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.10.010
更新日期：2007-12-07 00:00:00
abstract：:In order to colonize a niche and compete for scarce resources, microorganisms have evolved means to adjust the expression levels of their biosynthetic enzymes in response to the changing levels of metabolites available to them. To do so, they often rely on transcription factors or structured RNAs that directly sense t...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2016.04.019
更新日期：2016-05-22 00:00:00
abstract：:In eukaryotes the MSH2-MSH3 and MSH2-MSH6 heterodimers initiate mismatch repair (MMR) by recognizing and binding to DNA mismatches. The MLH1-PMS1 heterodimer then interacts with the MSH proteins at or near the mismatch site and is thought to act as a mediator to recruit downstream repair proteins. Here we analyzed fiv...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(03)00694-6
更新日期：2003-08-01 00:00:00
abstract：:We have developed a formalism and a computational method for analyzing the potential functional consequences of non-synonymous single nucleotide polymorphisms. Our approach uses a structural model and phylogenetic information to derive a selection of structure and sequence-based features serving as indicators of an am...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.4510
更新日期：2001-03-23 00:00:00
abstract：:The interaction of the two binding sites of the starch-binding domain (SBD) of Aspergillus niger glucoamylase 1 (GA-I) with substrate has been investigated by using atomic force microscopy (AFM) and UV difference spectroscopy in combination with site-specific mutants of both SBD and GA-I. The SBD possesses two binding...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5097
更新日期：2001-11-09 00:00:00
abstract：:The Escherichia coli T4 bacteriophage uses two glycosyltransferases to glucosylate and thus protect its DNA: the retaining alpha-glucosyltransferase (AGT) and the inverting beta-glucosyltransferase (BGT). They glucosylate 5-hydroxymethyl cytosine (5-HMC) bases of duplex DNA using UDP-glucose as the sugar donor to form...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.07.007
更新日期：2005-09-09 00:00:00
abstract：:Crystals of the apo form of the vitamin B12 and colicin receptor, BtuB, that diffract to 1.95 A have been grown by the membrane-based in meso technique. The structure of the protein differs in several details from that of its counterpart grown by the more traditional, detergent-based (in surfo) method. Some of these d...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.09.022
更新日期：2006-12-08 00:00:00
abstract：:The importance of including different energy contributions in calculations of electrostatic energies in proteins is examined by calculating the intrinsic pKa values of the acidic groups of bovine pancreatic trypsin inhibitor. It appears that such calculations provide a powerful and revealing test; the relevant solvati...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90411-5
更新日期：1985-09-20 00:00:00
abstract：:Transfer RNA su7 G36 is a derivative of tRNA(Trp) with a 3'GUC anticodon complementary to the glutamine codon CAG. This tRNA requires a normally forbidden G-U wobble at the first codon position to suppress a UAG (amber) termination codon. Measurement of amber suppression by mutated su7 G36 tRNAs and correction for tRN...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1095
更新日期：1994-02-04 00:00:00
abstract：:The reverse transcriptase (RT) of HIV-1 and feline immunodeficiency virus (FIV) consist of two subunits of 51 kDa (p51) and 66 kDa (p66). In order to elucidate the role of p51 in the heterodimer, chimeric HIV-1/FIV RT heterodimers were constructed and characterized. The FIV RT p51/HIV-1 RT p66 chimera showed a 2.5-fol...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.1739
更新日期：1998-05-15 00:00:00
abstract：:Previous studies show that some yeast strains carrying point mutations of domain 5 that block splicing of a mitochondrial group II intron yield spontaneous revertants in which splicing is partially restored by dominant mutations of nuclear genes. Here we cloned and sequenced the suppressor allele of one such gene, and...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2021
更新日期：1998-09-25 00:00:00
abstract：:The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(92)90637-y
更新日期：1992-08-05 00:00:00
abstract：:alpha-Synuclein (alpha-syn) is a 140-residue protein of unknown function, involved in several neurodegenerative disorders, such as Parkinson's disease. Recently, the possible interaction between alpha-syn and polyunsaturated fatty acids has attracted a strong interest. Indeed, lipids are able to trigger the multimeriz...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2009.09.008
更新日期：2009-11-20 00:00:00
abstract：:Human islet amyloid polypeptide (hIAPP) is a highly amyloidogenic protein co-secreted with insulin in response to glucose levels. The formation of hIAPP amyloid plaques near islet cells has been linked to the death of insulin-secreting β-cells in humans and the progression of type II diabetes. Since both healthy indiv...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2011.05.015
更新日期：2011-07-08 00:00:00
abstract：:Numerous physical and genetic approaches have identified residues in the alpha, beta, beta' and sigma subunits of Escherichia coli RNA polymerase that are involved in transcriptional processes; in contrast, relatively little data exist to demonstrate interacting regions within or between the subunits themselves. As a ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0244
更新日期：1996-05-03 00:00:00
abstract：:Silk fibroin with the alanyl carboxyl carbon enriched with 13C was obtained by giving a diet containing 13C-enriched alanine to the larvae of Bombyx mori and Antheraea pernyi at the fifth instar. Sericin-free fibroin fibers were prepared from cocoons, and gut was made from the liquid silk in the gland. The final 13C c...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(86)90414-6
更新日期：1986-01-05 00:00:00
