Parasitoids of the ladybird beetles (Coleoptera: Coccinellidae) in Iran: an update

Summary

Over the past few decades, many records of the parasitoids parasitizing Coccinellidae have been reported from Iran. Some of them, presented in hard to access conference proceedings, theses, older books and journal articles, were then inaccurately quoted in other papers. Furthermore, some other records were subsequently considered misidentifications and the corrected identity of the parasitoids was proposed in later published papers. Due to the accumulation of that misleading information, we decided to gather and critically evaluate all available Iranian data on the parasitoids of Coccinellidae. To the review presented here we also added new data on the parasitism of Coccinella septempunctata L. by a braconid Dinocampus coccinellae (Schrank) in the Lorestan province and on the parasitism of Hyperaspis pseudopustulata Mulsant by an encyrtid Homalotylus flaminius (Dalman) in the Kermanshah province. Hyperaspis pseudopustulata is a new host for H. flaminius, and is also a species new to the fauna of Iran. Altogether, our review revealed one species of dipteran and 16 species of hymenopteran parasitoids associated with Coccinellidae in Iran. The identity of some of those species, however, seems uncertain and should be re-examined.     

Structure-based Analysis of DNA Sequence Patterns Guiding Nucleosome Positioning in vitro

Abstract

Recent studies of genome-wide nucleosomal organization suggest that the DNA sequence is one of the major determinants of nucleosome positioning. Although the search for underlying patterns encoded in nucleosomal DNA has been going on for about 30 years, our knowledge of these patterns still remains limited. Based on our evaluations of DNA deformation energy, we developed new scoring functions to predict nucleosome positioning. There are three principal differences between our approach and earlier studies: (i) we assume that the length of nucleosomal DNA varies from 146 to 147 bp; (ii) we consider the anisotropic flexibility of pyrimidine-purine (YR) dimeric steps in the context of their neighbors (e.g., YYRR versus RYRY); (iii) we postulate that alternating AT-rich and GC-rich motifs reflect sequence-dependent interactions between histone arginines and DNA in the minor groove. Using these functions, we analyzed 20 nucleosome positions mapped in vitro at single nucleotide resolution (including clones 601, 603, 605, the pGUB plasmid, chicken β-globin and three 5S rDNA genes). We predicted 15 of the 20 positions with 1-bp precision, and two positions with 2-bp precision. The predicted position of the ‘601’ nucleosome (i.e., the optimum of the computed score) deviates from the experimentally determined unique position by no more than 1 bp—an accuracy exceeding that of earlier predictions.

Our analysis reveals a clear heterogeneity of the nucleosomal sequences which can be divided into two groups based on the positioning ‘rules’ they follow. The sequences of one group are enriched by highly deformable YR/YYRR motifs at the minor-groove bending sites SHL ±3.5 and ±5.5, which is similar to the α-satellite sequence used in most crystallized nucleosomes. Apparently, the positioning of these nucleosomes is determined by the interactions between histones H2A/H2B and the terminal parts of nucleosomal DNA. In the other group (that includes the ‘601’ clone) the same YR/YYRR motifs occur predominantly at the sites SHL ±1.5. The interaction between the H3/H4 tetramer and the central part of the nucleosomal DNA is likely to be responsible for the positioning of nucleosomes of this group, and the DNA trajectory in these nucleosomes may differ in detail from the published structures.

Thus, from the stereochemical perspective, the in vitro nucleosomes studied here follow either an X-ray-like pattern (with strong deformations in the terminal parts of nucleosomal DNA), or an alternative pattern (with the deformations occurring predominantly in the central part of the nucleosomal DNA). The results presented here may be useful for genome-wide classification of nucleosomes, linking together structural and thermodynamic characteristics of nucleosomes with the underlying DNA sequence patterns guiding their positions.     

Pulling the covers in electronic health records for an association study with self-reported sleep behaviors

ABSTRACT

The electronic health record (EHR) contains rich histories of clinical care, but has not traditionally been mined for information related to sleep habits. Here, we performed a retrospective EHR study based on a cohort of 3,652 individuals with self-reported sleep behaviors documented from visits to the sleep clinic. These individuals were obese (mean body mass index 33.6 kg/m²) and had a high prevalence of sleep apnea (60.5%), however we found sleep behaviors largely concordant with prior prospective cohort studies. In our cohort, average wake time was 1 hour later and average sleep duration was 40 minutes longer on weekends than on weekdays (p < 10^?12). Sleep duration varied considerably as a function of age and tended to be longer in females and in whites. Additionally, through phenome-wide association analyses, we found an association of long weekend sleep with depression, and an unexpectedly large number of associations of long weekday sleep with mental health and neurological disorders (q < 0.05). We then sought to replicate previously published genetic associations with morning/evening preference on a subset of our cohort with extant genotyping data (n = 555). While those findings did not replicate in our cohort, a polymorphism (rs3754214) in high linkage disequilibrium with a previously published polymorphism near TARS2 was associated with long sleep duration (p < 0.01). Collectively, our results highlight the potential of the EHR for uncovering the correlates of human sleep in real-world populations.     

Mathematical modeling of capillary formation and development in tumor angiogenesis: penetration into the stroma

The purpose of this paper is to present a mathematical model for the tumor vascularization theory of tumor growth proposed by Judah Folkman in the early 1970s and subsequently established experimentally by him and his coworkers [Ausprunk, D. H. and J. Folkman (1977) Migration and proliferation of endothelial cells in performed and newly formed blood vessels during tumor angiogenesis, Microvasc Res., 14, 53–65; Brem, S., B. A. Preis, ScD. Langer, B. A. Brem and J. Folkman (1997) Inhibition of neovascularization by an extract derived from vitreous Am. J. Opthalmol., 84, 323–328; Folkman, J. (1976) The vascularization of tumors, Sci. Am., 234, 58–64; Gimbrone, M. A. Jr, R. S. Cotran, S. B. Leapman and J. Folkman (1974) Tumor growth and neovascularization: an experimental model using the rabbit cornea, J. Nat. Cancer Inst., 52, 413–419]. In the simplest version of this model, an avascular tumor secretes a tumor growth factor (TGF) which is transported across an extracellular matrix (ECM) to a neighboring vasculature where it stimulates endothelial cells to produce a protease that acts as a catalyst to degrade the fibronectin of the capillary wall and the ECM. The endothelial cells then move up the TGF gradient back to the tumor, proliferating and forming a new capillary network. In the model presented here, we include two mechanisms for the action of angiostatin. In the first mechanism, substantiated experimentally, the angiostatin acts as a protease inhibitor. A second mechanism for the production of protease inhibitor from angiostatin by endothelial cells is proposed to be of Michaelis-Menten type. Mathematically, this mechanism includes the former as a subcase. Our model is different from other attempts to model the process of tumor angiogenesis in that it focuses (1) on the biochemistry of the process at the level of the cell; (2) the movement of the cells is based on the theory of reinforced random walks; (3) standard transport equations for the diffusion of molecular species in porous media. One consequence of our numerical simulations is that we obtain very good computational agreement with the time of the onset of vascularization and the rate of capillary tip growth observed in rabbit cornea experiments [Ausprunk, D. H. and J. Folkman (1977) Migration and proliferation of endothelial cells in performed and newly formed blood vessels during tumor angiogenesis, Microvasc Res., 14, 73–65; Brem, S., B. A. Preis, ScD. Langer, B. A. Brem and J. Folkman (1997) Inhibition of neovascularization by an extract derived from vitreous Am. J. Opthalmol., 84, 323–328; Folkman, J. (1976) The vascularization of tumors, Sci. Am., 234, 58–64; Gimbrone, M. A. Jr, R. S. Cotran, S. B. Leapman and J. Folkman (1974) Tumor growth and neovascularization: An experimental model using the rabbit cornea, J. Nat. Cancer Inst., 52, 413–419]. Furthermore, our numerical experiments agree with the observation that the tip of a growing capillary accelerates as it approaches the tumor [Folkman, J. (1976) The vascularization of tumors, Sci. Am., 234, 58–64]. An erratum to this article is available at .     

Structural Features of Glycera dibranchiata Monomer Hemoglobins. Primary Sequences of Monomer Hemoglobin Components II and III

Primary sequences for the remaining two members (GMH2, GMH3) of the group of three major monomeric hemoglobins from the marine annelid Glycera dibranchiata have been obtained. Full sequences of each 147-amino acid globin were achieved with a high degree of confidence using standard Edman technology in combination with molecular mass determinations of the intact globins and of the cyanogen bromide cleavage fragments using electrospray ionization mass spectrometry. When minor assumptions concerning Q/E identities are made these new results indicate the likely correspondence of GMG2 with the protein represented by the first Glycera dibranchiata monomer hemoglobin complete sequence [Imamura et al., (1972), J. Biol. Chem. 247, 2785–2797]. When these new sequences are combined with the previously determined primary sequence for the third major monomer hemoglobin, GMH4 [Alam et al., J. Protein Chem. (1994), 13, 151–164], it becomes clear that these three (GMG2–4) are truly distinct proteins, contrary to previous suggestions. Surprisingly, our results show that none of these three primary sequences is identical to the published sequence of the refined monomer hemoglobin crystal structure protein; however, there is a strong correspondence to the GMG2 sequence. The present sequencing results, in combination with the published GMH4 sequence, confirm the presence of a distal Leu in place of the more commonly encountered distal His in all three of the major monomer hemoglobins isolated in this laboratory and indicate that the unusual B10 Phe occurs only in GMH4. Analysis of the sequences presented here, along with comparison of amino acid content for Glycera dibranchiata monomer hemoglobins isolated from three different laboratories, and comparison of NMR results from two laboratories suggest further correspondences which unify disparate published isolations.     

氮依赖型甲烷厌氧氧化菌的整合

氮依赖型甲烷厌氧氧化菌(nitrite-dependent anaerobic methane oxidation bacteria,n-damo细菌,属于NC10门)是最近10年来微生物生态学领域的研究热点。然而,对该类群基于现有数据的生态分布、群落结构和系统进化的整合分析还未见报道。【目的】为了更好地将近年来针对该类群的研究做一次全面梳理,本文通过整合前人已有发表数据和结合自身实验数据两方面进行。【方法】一方面,利用NCBI数据库(数据搜集到2016年11月)中所有n-damo细菌序列对其进行生物信息学分析;另一方面,对大九湖泥炭地表层泥炭利用16S rRNA二代测序技术对该类群进行检测,并同前人数据进行对比。【结果】n-damo细菌主要在沉积物、湿地和水稻土检出;基于pmo A基因的n-damo细菌的平均检出率是基于16S rRNA基因检出率的7倍,但是这两类基因分子标记物所得到的多样性指数保持相对稳定(1.4-3.4);贫氮的大九湖泥炭其NC10的丰度仅为0.067%。【结论】n-damo类群种群相对稳定,暗示其行使的生态功能相对单一;贫氮的大九湖泥炭其极低的NC10丰度暗示氮对NC10是限制因子;具有真正氮依赖型甲烷厌氧氧化细菌的Group A可能只占很少的一部分(小于20%),暗示出该类群真正的生态潜能需要进一步评估。本次整合分析为更好的理解n-damo细菌的生活环境、评估不同基因分子标记物下n-damo细菌的检出率、不同亚类群比如Group A和Group B等的丰度和真正的潜在生态功能提供参考。     

Drug response prediction using graph representation learning and Laplacian feature selection

Background

Essential proteins are indispensable to the development and survival of cells. The identification of essential proteins not only is helpful for the understanding of the minimal requirements for cell survival, but also has practical significance in disease diagnosis, drug design and medical treatment. With the rapidly amassing of protein–protein interaction (PPI) data, computationally identifying essential proteins from protein–protein interaction networks (PINs) becomes more and more popular. Up to now, a number of various approaches for essential protein identification based on PINs have been developed.

Results

In this paper, we propose a new and effective approach called iMEPP to identify essential proteins from PINs by fusing multiple types of biological data and applying the influence maximization mechanism to the PINs. Concretely, we first integrate PPI data, gene expression data and Gene Ontology to construct weighted PINs, to alleviate the impact of high false-positives in the raw PPI data. Then, we define the influence scores of nodes in PINs with both orthological data and PIN topological information. Finally, we develop an influence discount algorithm to identify essential proteins based on the influence maximization mechanism.

Conclusions

We applied our method to identifying essential proteins from saccharomyces cerevisiae PIN. Experiments show that our iMEPP method outperforms the existing methods, which validates its effectiveness and advantage.

     

Developing a Tool for Increasing the Awareness about Gendered and Intersectional Processes in the Clinical Assessment of Patients – A Study of Pain Rehabilitation

ObjectiveThere is a need for tools addressing gender inequality in the everyday clinical work in health care. The aim of our paper was to develop a tool for increasing the awareness of gendered and intersectional processes in clinical assessment of patients, based on a study of pain rehabilitation.MethodsIn the overarching project named “Equal care in rehabilitation” we used multiple methods (both quantitative and qualitative) in five sub studies. With a novel approach we used Grounded Theory in order to synthesize the results from our sub studies, in order to develop the gender equality tool. The gender equality tool described and developed in this article is thus based on results from sub studies about the processes of assessment and selection of patients in pain rehabilitation. Inspired by some questions in earlier tools, we posed open ended questions and inductively searched for findings and concepts relating to gendered and social selection processes in pain rehabilitation, in each of our sub studies. Through this process, the actual gender equality tool was developed as 15 questions about the process of assessing and selecting patients to pain rehabilitation. As a more comprehensive way of understanding the tool, we performed a final step of the GT analyses. Here we synthesized the results of the tool into a comprehensive model with two dimensions in relation to several possible discrimination axes.ResultsThe process of assessing and selecting patients was visualized as a funnel, a top down process governed by gendered attitudes, rules and structures. We found that the clinicians judged inner and outer characteristics and status of patients in a gendered and intersectional way in the process of clinical decision-making which thus can be regarded as (potentially) biased with regard to gender, socio-economic status, ethnicity and age.ImplicationsThe clinical implications of our tool are that the tool can be included in the systematic routine of clinical assessment of patients for both awareness raising and as a base for avoiding gender bias in clinical decision-making. The tool could also be used in team education for health professionals as an instrument for critical reflection on gender bias.ConclusionsThus, tools for clinical assessment can be developed from empirical studies in various clinical settings. However, such a micro-level approach must be understood from a broader societal perspective including gender relations on both the macro- and the meso-level.     

Pathway analysis for intracellular Porphyromonas gingivalis using a strain ATCC 33277 specific database

Background  

Porphyromonas gingivalis is a Gram-negative intracellular pathogen associated with periodontal disease. We have previously reported on whole-cell quantitative proteomic analyses to investigate the differential expression of virulence factors as the organism transitions from an extracellular to intracellular lifestyle. The original results with the invasive strain P. gingivalis ATCC 33277 were obtained using the genome sequence available at the time, strain W83 [GenBank: AE015924]. We present here a re-processed dataset using the recently published genome annotation specific for strain ATCC 33277 [GenBank: AP009380] and an analysis of differential abundance based on metabolic pathways rather than individual proteins.     

Evolutionary history and systematics of Acer section Acer – a case study of low-level phylogenetics

The phylogenetic and systematic position of all species of Acer section Acer from North America, East Asia, and western Eurasia are evaluated using various splits-based networks (distance networks, bipartition networks), ITS motif analysis, and morphology. Molecular analyses are based on 276 ITS clones obtained from 101 specimens collected mainly from natural stands. The large sample size ensures to cover sufficiently inter- and intraspecific ITS variability of this group. Formerly recognised species are generally supported by ITS data and morphology; the combination of molecular (ITS) and morphological criteria allows defining seven (supraspecific) taxonomic groups prior to a phylogenetic reconstruction. Phylogenetic signals captured in modern ITS sequences are partly incompatible but clearly suggest that Acer section Acer underwent three major radiations. Horizontal gene flow is indicated between ancestors of extant taxa that are isolated at present times. The level of ITS derivation can be estimated and corresponds to levels of morphological differentiation and (palaeo-) biogeographical patterns. Based on our results we question the potential of cladistic approaches to infer low-level evolution in an adequate manner and demonstrate that speciation in members of Acer section Acer is not generally linked to cladogenesis. The data and methodologies provided here allow to trace pathways of low-level evolution and to analyse such data sets with a less restricted (non-dichotomous) dynamic concept. Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Seed-shedding in heather (Calluna vulgaris (L.) Hull

Abstract

Background: Accumulating evidence, mainly from small-scale experiments, suggests that species diversity helps stabilise ecological communities; however, this relationship needs testing at larger scales in a wider range of natural communities.

Aims: In experimentally burnt ericaceous shrub stands, we aimed to determine whether more diverse stands had more stable vegetation cover.

Methods: Using two prescribed fire management experiments – one on heathland and one in forest – at scales of 100–700 m², we compared pre-disturbance vegetation characteristics (measures of diversity, traits and composition) with resistance (degree of perturbation on disturbance), resilience (here defined as post-disturbance recovery rate) and stability (the inverse of temporal variability).

Results: Responses to disturbance were usually best explained by a measure of dominance: Simpson's index. High dominance was associated with high resilience, but low resistance and low stability. Within the forest, the shrub community had lower dominance and higher stability than it did on heathland. Dominance and diversity were strongly linked as opposite poles of a principal axis of vegetation variation; therefore, more diverse vegetation was more stable.

Conclusions: Ericaceous shrub cover is known to support important ecosystem services, such as soil protection, carbon sequestration, flood prevention and livestock grazing. Our results suggest that high shrub diversity would support stable provision of these services. Land managers who prioritise this aim in British heathlands and pinewoods should consider a wider range of management approaches than those of typical current practice.     

Consistent probabilistic outputs for protein function prediction

Background:

The wide availability of genome-scale data for several organisms has stimulated interest in computational approaches to gene function prediction. Diverse machine learning methods have been applied to unicellular organisms with some success, but few have been extensively tested on higher level, multicellular organisms. A recent mouse function prediction project (MouseFunc) brought together nine bioinformatics teams applying a diverse array of methodologies to mount the first large-scale effort to predict gene function in the laboratory mouse.

Results:

In this paper, we describe our contribution to this project, an ensemble framework based on the support vector machine that integrates diverse datasets in the context of the Gene Ontology hierarchy. We carry out a detailed analysis of the performance of our ensemble and provide insights into which methods work best under a variety of prediction scenarios. In addition, we applied our method to Saccharomyces cerevisiae and have experimentally confirmed functions for a novel mitochondrial protein.

Conclusion:

Our method consistently performs among the top methods in the MouseFunc evaluation. Furthermore, it exhibits good classification performance across a variety of cellular processes and functions in both a multicellular organism and a unicellular organism, indicating its ability to discover novel biology in diverse settings.

     

Best Practice Guidelines on Informed Consent for Weight Loss Surgery Patients

Objective: To provide evidence‐based guidelines on informed consent and the education that underlies it for legally competent, severely obese weight loss surgery (WLS) patients. Research Methods and Procedures: We conducted a systematic review of the scientific literature published on MEDLINE between 1984 and 2004. Three articles focused on informed consent for WLS; none was based on empirical studies. We summarized each paper and assigned evidence categories according to a grading system derived from established evidence‐based models. We also relied on informed consent and educational materials from six WLS programs in Massachusetts. All evidence is Category D. Recommendations were based on a review of the available literature, informed consent materials from WLS programs, and expert opinion. Results: This Task Group found that the informed consent process contributes to long‐term outcome in multiple ways but is governed by limited legal requirements. We focused our report on the legal and ethical issues related to informed consent, i.e., disclosure vs. comprehension. Recommendations centered on the importance of assessing patient comprehension of informed consent materials, the content of those materials, and the use of active teaching/learning techniques to promote understanding. Discussion: Although demonstrated comprehension is not a legal requirement for informed consent in Massachusetts or other states, the members of this Task Group found that the best interests of WLS patients, providers, and facilities are served when clinicians engage patients in active learning and collaborative decision making.     

Species-rich Nardus stricta grasslands host a higher vascular plant diversity on calcareous than on siliceous bedrock

Background: Species-rich Nardus stricta grasslands are a priority habitat for conservation in Europe. They typically occur on siliceous substrates and less frequently are found on calcareous bedrock.

Aims: The present paper aimed to identify the environmental factors (i.e. bedrock type, topographic, and climatic factors) that are related with community diversity and to assess if differences in plant diversity between N. stricta communities on calcareous and siliceous bedrock occur. We hypothesised that Nardus grasslands on calcareous bedrock hosted a higher vascular plant diversity than those on siliceous bedrock.

Methods: Based on 579 vegetation surveys carried out in the south-western Alps, we assessed vascular plant diversity (species richness, Shannon diversity, and Pielou’s equitability index) of species-rich Nardus grasslands and compared it between N. stricta communities on calcareous and siliceous bedrock.

Results: Elevation was identified as the main factor related to species composition, while species diversity was mostly related to mean annual precipitation and bedrock type. Species richness, Shannon diversity, and Pielou’s equitability index were higher within the communities on calcareous rather than on siliceous bedrock and a total of 89 and 34 indicator species were detected, respectively.

Conclusions: Based on our results, we suggest to protect primarily, as a habitat of priority interest, N. stricta grasslands on calcareous substrates for the higher vascular plant diversity hosted.     

MCMC for hidden Markov models incorporating aggregation of states and filtering

This paper is concerned with the statistical analysis of single ion channel records. Single channels are modelled by using hidden Markov models and a combination of Bayesian statistics and Markov chain Monte Carlo methods. The techniques presented here provide a straightforward generalization to those in Rosales et al. (2001, Biophys. J., 80, 1088–1103), allowing to consider constraints imposed by a gating mechanism such as the aggregation of states into classes. This paper also presents an extension that allows to consider correlated background noise and filtered data, extending the scope of the analysis toward real experimental conditions. The methods described here are based on a solid probabilistic basis and are less computationally intensive than alternative Bayesian treatments or frequentist approaches that consider correlated data.     

The integrin-linked kinase gene up-regulated by hypoxia plays its pro-survival role in colorectal cancer cells

Abstract

Context: Colorectal cancer (CRC) is a leading cause of cancer death in recent years. It is believed that there are hypoxic regions in both early and advanced stage of tumor and hypoxia is able to reinforce the aggressiveness of tumor cells and accelerate the progression of cancer. Objective: Until now the mechanisms by which hypoxia promotes the progression of CRC are far from well understood. Integrin-linked kinase (ILK) is a crucial mediator and over-expressed in CRC patients. But whether ILK is involved in the process that hypoxia promotes CRC cells growth and silencing the ILK gene results in CRC cells apoptosis is not clear. Materials and methods: Lentivirus transfection, invasion assay, TUNEL assay, Bromodeoxyuridine incorporation and mitochondrial function assay were applied to demonstrate our hypothesis. Results: In this study, we found that hypoxia induced the expression of ILK in a time-dependent manner, and after knocking down ILK expression with ILK shRNA, the cells proliferation promoted by hypoxia was inhibited in HT29 cell line. Moreover, blocking the ILK pathway led to caspase-3 and caspase-9 activations, the decrease of mitochondrial membrane potential, and cells apoptosis. And the inhibitory effects of hypoxia on cells apoptosis were mediated by the ILK pathway. In addition, hypoxia promoted HT29 cells metastasis and invasion through the ILK pathway. Conclusions: Therefore, we conclude that the CRC cells survival and invasion enhanced by hypoxia are mediated by ILK, and ILK may be an important potential therapeutic target for CRC.     

The burden of rare cancer in Japan: Application of the RARECARE definition

BackgroundDespite the fact that rare cancer is a new target of cancer control in Japan, the incidence of rare cancers is unknown and there is no generally accepted definition of rare cancers in this country. With the aim of calculating incidences of rare cancers in Japan, we therefore adopted a definition and classification of rare cancers that had been published in the European Union (EU) in 2011.MethodsUsing incidence data between 1998 and 2007 submitted by 12 of population based cancer registries in Japan that met our quality criteria and drawing on the EU definition (incidence <6 per 100,000 per year), we estimated the incidences of 845 combinations of tumor sites and histological groups and thus identified the cancers that are rare in Japan.ResultsAfter identifying 193 combinations of tumor sites and histological groups that fit our criteria for rare cancers, we estimated their incidence to be about 75 per 100,000, which corresponds to about 94,800 new diagnoses in 2012 or approximately 15% of all cancer diagnoses. The categorization of rare and common cancers was almost the same in Japan as in EU.ConclusionsThe present study provides an indication of the size of the rare cancer burden in Japan and epidemiological information to explore this. We are expecting further discussion based on our results with stakeholders in order to construct a Japanese definition of rare cancers.     

Crystal structure of A. aeolicus LpxC with bound product suggests alternate deacetylation mechanism

UDP‐3‐O‐acyl‐N‐acetylglucosamine deacetylase (LpxC) is the first committed step to form lipid A, an essential component of the outer membrane of Gram‐negative bacteria. As it is essential for the survival of many pathogens, LpxC is an attractive target for antibacterial therapeutics. Herein, we report the product‐bound co‐crystal structure of LpxC from the acheal Aquifex aeolicus solved to 1.6 Å resolution. We identified interactions by hydroxyl and hydroxymethyl substituents of the product glucosamine ring that may enable new insights to exploit waters in the active site for structure‐based design of LpxC inhibitors with novel scaffolds. By using this product structure, we have performed quantum mechanical modeling on the substrate in the active site. Based on our results and published experimental data, we propose a new mechanism that may lead to a better understanding of LpxC catalysis and inhibition. Proteins 2015; 83:1706–1719. © 2015 Wiley Periodicals, Inc.