Abstract:
:β-Lactamases are a major threat to the clinical use of carbapenems, which are often antibiotics of last resort. Despite this, the reaction outcomes and mechanisms by which β-lactamases degrade carbapenems are still not fully understood. The carbapenem bicyclic core consists of a β-lactam ring fused to a pyrroline ring. Following β-lactamase-mediated opening of the β-lactam, the pyrroline may interconvert between an enamine (2-pyrroline) form and two epimeric imine (1-pyrroline) forms; previous crystallographic and spectroscopic studies have reported all three of these forms in the contexts of hydrolysis by different β-lactamases. As we show by NMR spectroscopy, the serine β-lactamases (KPC-2, SFC-1, CMY-10, OXA-23, and OXA-48) and metallo-β-lactamases (NDM-1, VIM-1, BcII, CphA, and L1) tested all degrade carbapenems to preferentially give the Δ2 (enamine) and/or (R)-Δ1 (imine) products. Rapid non-enzymatic tautomerisation of the Δ2 product to the (R)-Δ1 product prevents assignment of the nascent enzymatic product by NMR. The observed stereoselectivity implies that carbapenemases control the form of their pyrroline ring intermediate(s)/product(s), thereby preventing pyrroline tautomerisation from inhibiting catalysis.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Lohans CT,Freeman EI,Groesen EV,Tooke CL,Hinchliffe P,Spencer J,Brem J,Schofield CJdoi
10.1038/s41598-019-49264-0subject
Has Abstractpub_date
2019-09-20 00:00:00pages
13608issue
1issn
2045-2322pii
10.1038/s41598-019-49264-0journal_volume
9pub_type
杂志文章abstract::Graphene grown directly on germanium is a possible route for the integration of graphene into nanoelectronic devices as well as it is of great interest for materials science. The morphology of the interface between graphene and germanium influences the electronic properties and has not already been completely elucidat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-48998-1
更新日期:2019-08-29 00:00:00
abstract::Modern sugarcane is an unusually complex heteroploid crop, and its genome comprises two or three subgenomes. To reduce the complexity of sugarcane genome research, the ploidy level and number of chromosomes can be reduced using flow chromosome sorting. However, a cell cycle synchronization (CCS) protocol for Saccharum...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-62086-9
更新日期:2020-03-19 00:00:00
abstract::Dysregulation of dopaminergic system induced by HIV-1 Tat protein-mediated direct inhibition of the dopamine transporter (DAT) has been implicated as a mediating factor of HIV-1 associated neurocognitive disorders. We have reported that single point mutations on human DAT (hDAT) at tyrosine88 (Y88F), lysine92 (K92M), ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39872-1
更新日期:2019-03-07 00:00:00
abstract::Heat shock factor-1 (HSF1) protects neurons from death caused by the accumulation of misfolded proteins by stimulating the transcription of genes encoding heat shock proteins (HSPs). This stimulatory action depends on the association of trimeric HSF1 to sequences within HSP gene promoters. However, we recently describ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-35610-1
更新日期:2018-11-22 00:00:00
abstract::Synthesis of homogenous glycans in quantitative yields represents a major bottleneck to the production of molecular tools for glycoscience, such as glycan microarrays, affinity resins, and reference standards. Here, we describe a combined biological/enzymatic synthesis that is capable of efficiently converting microbi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-15891-8
更新日期:2017-11-21 00:00:00
abstract::A series of edge-selectively halogenated (X = Cl, Br, I) graphene nanoplatelets (XGnPs = ClGnP, BrGnP, IGnP) were prepared simply by ball-milling graphite in the presence of Cl2, Br2 and I2, respectively. High BET surface areas of 471, 579 and 662 m(2)/g were observed for ClGnP, BrGnP and IGnP, respectively, indicatin...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01810
更新日期:2013-01-01 00:00:00
abstract::Precision Medicine in Oncology requires tailoring of therapeutic strategies to individual cancer patients. Due to the limited quantity of tumor samples, this proves to be difficult, especially for early stage cancer patients whose tumors are small. In this study, we exploited a 2.4 × 2.4 centimeters polydimethylsiloxa...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-08831-z
更新日期:2017-08-22 00:00:00
abstract::Two series of Ge0.8Sn0.2 samples were grown on Ge buffered Si substrate by molecular beam epitaxy (MBE) to investigate the influence of growth temperature and film thickness towards the evolution of surface morphology. A novel phenomena was observed that the Ge0.8Sn0.2 film was segregated and relaxed by the formation ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-63152-y
更新日期:2020-04-09 00:00:00
abstract::Groundwater aquifers are an essential source of drinking water, and must be protected against contamination. Phosphogypsum stacks originating from the processing of phosphate rock contain small amounts of radionuclides, such as 226Ra. In September 2016, a sinkhole located beneath a phosphogypsum stack collapsed under ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-29541-0
更新日期:2018-07-30 00:00:00
abstract::Adolescence is a critical period for the development of higher-order cognitive functions. Unlike in humans, very limited tools are available to assess such cognitive abilities in adolescent rodents. We implemented a modified 5-Choice Serial Reaction Time Task (5CSRTT) to selectively measure attentiveness, impulsivity,...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10112-8
更新日期:2017-08-30 00:00:00
abstract::Heterostructures based on two-dimensional (2D) materials have sparked wide interests in both fundamental physics and applied devices. Recently, Dirac/Weyl semimetals are emerging as capable functional materials for optoelectronic devices. However, thus far the interfacial coupling of an all-semimetal 2D heterostructur...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-29717-8
更新日期:2018-08-27 00:00:00
abstract::Olfactory dysfunction is a robust and early sign for Parkinson's disease (PD). Previous studies have revealed its association with dementia and related neural changes in PD. Yet, how olfactory dysfunction affects white matter (WM) microstructure in newly diagnosed and untreated PD remains unclear. Here we comprehensiv...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-12947-7
更新日期:2017-10-02 00:00:00
abstract::The current anaesthesia information management system (AIMS) has limited capability for the acquisition of high-quality vital signs data. We have developed a Vital Recorder program to overcome the disadvantages of AIMS and to support research. Physiological data of surgical patients were collected from 10 operating ro...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-20062-4
更新日期:2018-01-24 00:00:00
abstract::Across the planet the biogeographic distribution of human cultural diversity tends to correlate positively with biodiversity. In this paper we focus on the biogeographic distribution of mammal species and human cultural diversity. We show that not only are these forms of diversity similarly distributed in space, but t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-76658-2
更新日期:2020-11-12 00:00:00
abstract::Whole-room indirect calorimeters (WRICs) have traditionally been used for real-time resting metabolic rate (RMR) measurements, while metabolic rate (MR) during short-interval exercises has commonly been measured by metabolic carts (MCs). This study aims to investigate the feasibility of incorporating short-interval ex...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71001-1
更新日期:2020-08-31 00:00:00
abstract::Maternal obesity is associated with lower basal plasma cortisol levels and increased risk of postpartum psychiatric disorders. Given that both obesity and the peripartum period are characterized by an imbalance between adrenocorticotropic hormone (ACTH) and cortisol, we hypothesized that the adrenal glands undergo per...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep14821
更新日期:2015-10-07 00:00:00
abstract::Studies reveal that there exists much interaction and communication between bacterial cells, with parts of these social behaviors depending on cell-cell contacts. The cell-cell contact has proved to be crucial for determining various biochemical processes. However, for cell culture with relatively low cell concentrati...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01993
更新日期:2013-01-01 00:00:00
abstract::Sentinel lymph node (SLN) mapping using dye or radioisotopes has been performed in patients with uterine cancer. Superparamagnetic iron oxide (SPIO) can be handled safely and is taken up by lymph nodes (LNs); however, its efficacy in detecting SLNs in uterine cancer remains unknown. This pilot study evaluated the use ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-64926-0
更新日期:2020-05-14 00:00:00
abstract::Long-read sequencing technologies such as Pacific Biosciences and Oxford Nanopore MinION are capable of producing long sequencing reads with average fragment lengths of over 10,000 base-pairs and maximum lengths reaching 100,000 base- pairs. Compared with short reads, the assemblies obtained from long-read sequencing ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03996-z
更新日期:2017-06-21 00:00:00
abstract::The PRL phosphatases are oncogenic when overexpressed but their in vivo biological function is less well understood. Previous gene deletion study revealed a role for PRL2 in spermatogenesis. We report here the first knockout mice lacking PRL1, the most related homolog of PRL2. We found that loss of PRL1 does not affec...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34211
更新日期:2016-09-26 00:00:00
abstract::Processing the meaning of action language correlates with somatotopic activity in premotor cortex (PMC). A previous neurostimulation study supported a causal contribution of PMC activity to action verb understanding, but the direction of the effect was unexpected: inhibiting PMC made participants respond faster to act...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-29600-6
更新日期:2018-07-30 00:00:00
abstract::Cell lytic enzymes represent an alternative to chemical decontamination or use of antibiotics to kill pathogenic bacteria, such as listeria. A number of phage cell lytic enzymes against listeria have been isolated and possess listericidal activity; however, there has been no attempt to incorporate these enzymes onto s...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01584
更新日期:2013-01-01 00:00:00
abstract::Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. HFMD outbreaks and reported cases have sharply increased in China since 2008. Epidemiological and clinical data of HFMD cases reported in Henan Province were collected from 2008 to 2013. Clinical specimens were obtained from a ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08904
更新日期:2015-03-10 00:00:00
abstract::A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-24796-z
更新日期:2018-04-19 00:00:00
abstract::Previous studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17-secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with an...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-26194-x
更新日期:2018-05-17 00:00:00
abstract::The strong age dependency of neonatal systemic infection with Escherichia coli K1 can be replicated in the neonatal rat. Gastrointestinal (GI) colonization of two-day-old (P2) rats leads to invasion of the blood within 48 h of initiation of colonization; pups become progressively less susceptible to infection over the...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00123-w
更新日期:2017-03-06 00:00:00
abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-22372-z
更新日期:2018-03-06 00:00:00
abstract::Leaf flattening influences plant photosynthesis, thereby affecting product yield and quality. Here, we obtained a stably inherited leaf crinkled mutant (lcm), derived from the Chinese cabbage doubled haploid (DH) 'FT' line using EMS mutagenesis combined with isolated microspore culture. The crinkled phenotype was cont...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-70975-2
更新日期:2020-08-18 00:00:00
abstract::Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep46166
更新日期:2017-04-11 00:00:00
abstract::We demonstrate a designed interaction between two isolated cell populations of Euglena gracilis and Chlamydomonas reinhardtii, separately confined in two 25-square micro-aquariums of lab-on-chip size. The interaction was realized by interlinking two identical optical feedback systems, which measured the cell distribut...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24602
更新日期:2016-04-21 00:00:00