检索结果-内蒙古大学图书馆

Crucial Roles of Two Hydrated Mg²⁺ Ions in Reaction Catalysis of the Pistol Ribozyme

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2020年第7期59卷 2837-2843页

作者： Teplova, Marianna Falschlunger, Christoph Krasheninina, Olga Egger, Michaela Ren, Aiming Patel, Dinshaw J. Micura, Ronald Leopold Franzens Univ Inst Organ Chem Innrain 80-82 A-6020 Innsbruck Austria Leopold Franzens Univ Ctr Mol Biosci Innrain 80-82 A-6020 Innsbruck Austria Mem Sloan Kettering Canc Ctr Struct Biol Program New York NY 10065 USA Zhejiang Univ Life Sci Inst Hangzhou 310058 Zhejiang Peoples R China

Pistol ribozymes constitute a new class of small self-cleaving RNAs. Crystal structures have been solved, providing three-dimensional snapshots along the reaction coordinate of pistol phosphodiester cleavage, corresponding to the pre-catalytic state, a vanadate mimic of the transition state, and the product. The results led to the proposed underlying chemical mechanism. Importantly, a hydrated Mg2+ ion remains innersphere-coordinated to N7 of G33 in all three states, and is consistent with its likely role as acid in general acid base catalysis (delta and beta catalysis). Strikingly, the new structures shed light on a second hydrated Mg2+ ion that approaches the scissile phosphate from its binding site in the pre-cleavage state to reach out for water-mediated hydrogen bonding in the cyclophosphate product. The major role of the second Mg2+ ion appears to be the stabilization of product conformation. This study delivers a mechanistic understanding of ribozyme-catalyzed backbone cleavage.

关键词： magnesium oligonucleotides reaction mechanisms RNA structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

Microbial community composition, and not pH, influences lake sediment function

引用

ECOSPHERE 2022年第5期13卷

作者： Bertolet, Brittni L. Louden, Sydney, I Jones, Stuart E. Univ Notre Dame Dept Biol Sci Notre Dame IN 46556 USA

Lake sediment microbial communities vary across ecosystems and are often differentiated across pH. Additionally, these pH-mediated differences in community composition are often correlated with changes in sediment functioning, such as methane and carbon dioxide production. However, few studies have experimentally tested pH effects on community assembly or considered how microbial community composition influences ecosystem function independent of differences in the environment. We used common garden experiments to test hypotheses about how pH influences microbial community assembly and function in lake sediments. Using inoculum from three acidic lakes and three near-neutral lakes, we found that both pH environment and inoculum source significantly influenced sediment microbial community assembly. However, inoculum source had a larger effect size for both the sediment methanogen and nonmethanogen communities, indicating important roles of dispersal and drift. Additionally, inoculum source, but not pH environment, significantly influenced sediment methane and carbon dioxide production. This research is one of the first to experimentally test the influence of pH on sediment microbial community composition, and in doing so, we show the community composition significantly influences sediment function independent of pH. Understanding how lake sediment microbial communities are influenced by environment is the first step toward mechanistically linking changes in community composition to ecosystem function, and we provide critical evidence for how changes in microbial community assembly with environmental change will likely alter carbon cycling in lake sediments.

关键词： lake methanogenesis microbial community assembly structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

Usage ofin situexopolysaccharide-forming lactic acid bacteria in food production: Meat products-A new field of application?

引用

COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY 2020年第6期19卷 2932-2954页

作者： Loeffler, Myriam Hilbig, Jonas Velasco, Lina Weiss, Jochen Univ Hohenheim Inst Food Sci & Biotechnol Dept Food Mat Sci Garbenstr 21-25 D-70599 Stuttgart Germany

In the meat industry, hydrocolloids and phosphates are used to improve the quality attributes of meat products. However, latest research results revealed that the usage of exopolysaccharide (EPS)-forming lactic acid bacteria (LAB), which are able to produce EPSin situduring processing could be an interesting alternative. The current review aims to give a better understanding of bacterial EPS production in food matrices with a special focus on meat products. This includes an introduction to microbial EPS production (homopolysaccharides as well as heteropolysaccharides) and an overview of parameters affecting EPS formation and yield depending on LAB used. This is followed by a summary of methods to detect and characterize EPS to facilitate a rational selection of starter cultures and fermentation conditions based on desired structure-function relationships in different food matrices. The mechanism of action ofin situgenerated EPS is then highlighted with an emphasis on different meat products. In the process, this review also highlights food additives currently used in meat production that could in the future be replaced byin situEPS-forming LAB.

关键词： exopolysaccharide detection in situexopolysaccharide production lactic acid bacteria meat quality structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

Constant pH molecular dynamics simulations: Current status and recent applications

引用

CURRENT OPINION IN STRUCTURAL BIOLOGY 2022年 77卷 102498页

作者： de Oliveira, Vinicius Martins Liu, Ruibin Shen, Jana Univ Maryland Dept Pharmaceut Sci Sch Pharm 20 Penn St Baltimore MD 20201 USA

Many important protein functions are carried out through proton-coupled conformational dynamics. Thus, the ability to accurately model protonation states dynamically has wide-ranging implications. Over the past two decades, two main types of constant pH methods (discrete and continuous) have been developed to enable proton-coupled molecular dynamics (MD) simulations. In this short review, we discuss the current status of the development and highlight recent applications that have advanced our understanding of protein structure-function relationships. We conclude the review by outlining the remaining challenges in the method development and projecting important areas for future applications.

关键词： Protein electrostatics Proton transfer structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

functional implications of pH-induced conformational changes in the Sphingosine kinase 1

引用

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2020年 225卷 117453页

作者： Gupta, Preeti Khan, Faez Iqbal Roy, Sonam Anwar, Saleha Dahiya, Rashmi Alajmi, Mohammed F. Hussain, Afzal Rehman, Md. Tabish Lai, Dakun Hassan, Md. Imtaiyaz Jamia Millia Islamia Ctr Interdisciplinary Res Basic Sci New Delhi 110025 India Univ Elect Sci & Technol China Sch Elect Sci & Engn Chengdu Sichuan Peoples R China King Saud Univ Coll Pharm Dept Pharmacognosy Riyadh Saudi Arabia

Sphingosine kinase 1 (SphK1) catalyzes the conversion of sphingosine to sphingosine-1-phosphate that acts as a bioactive signalling molecule, and regulates various cellular processes including lymphocyte trafficking, angiogenesis and response to apoptotic stimuli. Abnormal expression of SphK1 has been observed in a wide range of cancers highlighting their role in tumour growth and metastasis. This enzyme also plays a critical role in metabolic and inflammatory diseases, including pulmonary fibrosis, diabetic neuropathy and Alzheimer's disease. In the present study, we have investigated the structural and conformational changes in SphK1 at varying pH using various spectroscopic techniques. Consistent results were observed with the function of SphK1 at corresponding pH values. SphK1 maintains its secondary and tertiary structure in the pH range of 7.5-10.0. However, protein aggregation was observed in the acidic pH range (4.0-6.5). At pH 2.0, the SphK1 exists in the molten-globule state. Kinase assay also shows that SphK1 activity was optimal in the pH range of 7.5-8.5. To complement in vitro results, we have performed 100 ns molecular dynamics simulation to examine the effect of pH on the structural stability of SphK1 at molecular level. SphK1 maintains its native conformation in the alkaline pH range with some residual fluctuations detected at acidic pH. A considerable correlation was noticed between spectroscopic, enzymatic activity and MD simulation studies. pH dependent structural changes can be further implicated to understand its association with disease condition, and cellular homeostasis with respect to protein function under variable pH conditions. (C) 2019 Elsevier B.V. All rights reserved.

关键词： Sphingosine kinase 1 structure-function relationships Kinase activity Molecular dynamics simulation Structural genomics pH-induced denaturation

来源：评论

学校读者我要写书评

暂无评论

Accurate and efficient structure-based computational mutagenesis for modeling fluorescence levels of Aequorea victoria green fluorescent protein mutants

引用

PROTEIN ENGINEERING DESIGN & SELECTION 2020年第33期33卷 gzaa022页

作者： Masso, Majid George Mason Univ Sch Syst Biol Lab Struct Bioinformat 10900 Univ Blvd MS 5B3 Manassas VA 20110 USA

A computational mutagenesis technique was used to characterize the structural effects associated with over 46 000 single and multiple amino acid variants of Aequorea victoria green fluorescent protein (GFP), whose functional effects (fluorescence levels) were recently measured by experimental researchers. For each GFP mutant, the approach generated a single score reflecting the overall change in sequence-structure compatibility relative to native GFP, as well as a vector of environmental perturbation (EP) scores characterizing the impact at all GFP residue positions. A significant GFP structure-function relationship (P < 0.0001) was elucidated by comparing the sequence-structure compatibility scores with the functional data. Next, the computed vectors for GFP mutants were used to train predictive models of fluorescence by implementing random forest (RF) classification and tree regression machine learning algorithms. Classification performance reached 0.93 for sensitivity, 0.91 for precision and 0.90 for balanced accuracy, and regression models led to Pearson's correlation as high as r = 0.83 between experimental and predicted GFP mutant fluorescence. An RF model trained on a subset of over 1000 experimental single residue GFP mutants with measured fluorescence was used for predicting the 3300 remaining unstudied single residue mutants, with results complementing known GFP biochemical and biophysical properties. In addition, models trained on the subset of experimental GFP mutants harboring multiple residue replacements successfully predicted fluorescence of the single residue GFP mutants. The models developed for this study were accurate and efficient, and their predictions outperformed those of several related state-of-the-art methods.

关键词： GFP machine learning prediction structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

Individual differences in amygdala volumes predict changes in functional connectivity between subcortical and cognitive control networks throughout adolescence

引用

NEUROIMAGE 2022年 247卷 118852-118852页

作者： Taylor, Brittany K. Frenzel, Michaela R. Eastman, Jacob A. Embury, Christine M. Agcaoglu, Oktay Wang, Yu-Ping Stephen, Julia M. Calhoun, Vince D. Wilson, Tony W. Boys Town Natl Res Hosp Inst Human Neurosci Boys Town NE 68010 USA Creighton Univ Dept Pharmacol & Neurosci Omaha NE 68178 USA Univ Nebraska Dept Psychol Omaha NE 68182 USA Georgia State Univ Georgia Inst Technol Triinst Ctr Translat Res Neuroimaging & Data Sci Atlanta GA USA Emory Univ Atlanta GA 30322 USA Tulane Univ Dept Biomed Engn New Orleans LA 70118 USA Mind Res Network Albuquerque NM USA

Adolescence is a critical period of structural and functional neural maturation among regions serving the cognitive control of emotion. Evidence suggests that this process is guided by developmental changes in amygdala and striatum structure and shifts in functional connectivity between subcortical (SC) and cognitive control (CC) networks. Herein, we investigate the extent to which such developmental shifts in structure and function reciprocally predict one another over time. 179 youth (9-15 years-old) completed annual MRI scans for three years. Amygdala and striatum volumes and connectivity within and between SC and CC resting state networks were measured for each year. We tested for reciprocal predictability of within-person and between-person changes in structure and function using random-intercept cross-lagged panel models. Within-person shifts in amygdala volumes in a given year significantly and specifically predicted deviations in SC-CC connectivity in the following year, such that an increase in volume was associated with decreased SC-CC connectivity the following year. Deviations in connectivity did not predict changes in amygdala volumes over time. Conversely, broader group-level shifts in SC-CC connectivity were predictive of subsequent deviations in striatal volumes. We did not see any cross-predictability among amygdala or striatum volumes and within-network connectivity measures. Within-person shifts in amygdala structure year-to-year robustly predicted weaker SC-CC connectivity in subsequent years, whereas broader increases in SC-CC connectivity predicted smaller striatal volumes over time. These specific structure function relationships may contribute to the development of emotional control across adolescence.

关键词： Striatum Emotional control Development structure-function relationships Structural Equation Modeling (SEM) longitudinal

来源：评论

学校读者我要写书评

暂无评论

structure and kinetic properties of human d-aspartate oxidase, the enzyme-controlling d-aspartate levels in brain

引用

FASEB JOURNAL 2020年第1期34卷 1182-1197页

作者： Molla, Gianluca Chaves-Sanjuan, Antonio Savinelli, Antonio Nardini, Marco Pollegioni, Loredano Univ Insubria Dipartimento Biotecnol & Sci Vita Via JH Dunant 3 I-21100 Varese Italy Univ Milan Dipartimento Biosci Via Celoria 26 I-20133 Milan Italy

d-Amino acids are the "wrong" enantiomers of amino acids as they are not used in proteins synthesis but evolved in selected functions. On this side, d-aspartate (d-Asp) plays several significant roles in mammals, especially as an agonist of N-methyl-d-aspartate receptors (NMDAR), and is involved in relevant diseases, such as schizophrenia and Alzheimer's disease. In vivo modulation of d-Asp levels represents an intriguing task to cope with such pathological states. As little is known about d-Asp synthesis, the only option for modulating the levels is via degradation, which is due to the flavoenzyme d-aspartate oxidase (DASPO). Here we present the first three-dimensional structure of a DASPO enzyme (from human) which belongs to the d-amino acid oxidase family. Notably, human DASPO differs from human d-amino acid oxidase (attributed to d-serine degradation, the main coagonist of NMDAR) showing peculiar structural features (a specific active site charge distribution), oligomeric state and kinetic mechanism, and a higher FAD affinity and activity. These results provide useful insights into the structure-function relationships of human DASPO: modulating its activity represents now a feasible novel therapeutic target.

关键词： d-aspartate d-aspartate oxidase flavoprotein NMDA receptor structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

functional analysis of BRCA1 RING domain variants: computationally derived structural data can improve upon experimental features for training predictive models

引用

INTEGRATIVE BIOLOGY 2020年第9期12卷 233-239页

作者： Masso, Majid George Mason Univ Coll Sci Sch Syst Biol 10900 Univ BlvdMS 5B3 Manassas VA 20110 USA

Advancements in the interpretation of variants of unknown significance are critical for improving clinical outcomes. In a recent study, massive parallel assays were used to experimentally quantify the effects of missense substitutions in the RING domain of BRCA1 on E3 ubiquitin ligase activity as well as BARD1 RING domain binding. These attributes were subsequently used for training a predictive model of homology-directed DNA repair levels for these BRCA1 variants relative to wild type, which is critical for tumor suppression. Here, relative structural changes characterizing BRCA1 variants were quantified by using an efficient and cost-free computational mutagenesis technique, and we show that these features lead to improvements in model performance. This work underscores the potential for bench researchers to gain valuable insights from computational tools, prior to implementing costly and time-consuming experiments.

关键词： structure-function relationships computational mutagenesis variants homology-directed DNA repair machine learning prediction

来源：评论

学校读者我要写书评

暂无评论

Different phenotypic outcome due to site-specific phosphorylation in the cancer-associated NQO1 enzyme studied by phosphomimetic mutations

引用

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 2022年第0期729卷 000-000页

作者： Pacheco-Garcia, Juan Luis Anoz-Carbonell, Ernesto Loginov, Dmitry S. Vankova, Pavla Salido, Eduardo Man, Petr Medina, Milagros Palomino-Morales, Rogelio Pey, Angel L. Univ Granada Dept Quim Fis Ave Fuentenueva S-N Granada 18071 Spain Univ Zaragoza Fac Ciencias Dept Bioquim & Biol Mol & Cellular Inst Biocomp & Fis Sistemas Complejos BIFIGBsC CS Zaragoza 50009 Spain Acad Sci Czech Republ Inst Microbiol BioCeV Prumyslova 595 Vestec 25250 Czech Republic Acad Sci Czech Republ Inst Biotechnol BioCeV Prumyslova 595 Vestec 25250 Czech Republic Univ La Laguna Hosp Univ Canarias Ctr Rare Dis CIBERER Tenerife 38320 Spain Univ Granada Fac Sci Dept Biochem & Mol Biol 1 Granada Spain Univ Granada Biomed Res Ctr CIBM Granada Spain Univ Granada Dept Quim Fis Un Excelencia Quim Aplicada Biomed & Medioambiente Ave Fuentenueva S-N Granada 18071 Spain Univ Granada Inst Biotecnol Ave Fuentenueva S-N Granada 18071 Spain

Protein phosphorylation is a common phenomenon in human flavoproteins although the functional consequences of this site-specific modification are largely unknown. Here, we evaluated the effects of site-specific phosphorylation (using phosphomimetic mutations at sites S40, S82 and T128) on multiple functional aspects as well as in the structural stability of the antioxidant and disease-associated human flavoprotein NQO1 using biophysical and biochemical methods. In vitro biophysical studies revealed effects of phosphorylation at different sites such as decreased binding affinity for FAD and structural stability of its binding site (S82), conformational stability (S40 and S82) and reduced catalytic efficiency and functional cooperativity (T128). Local stability measurements by H/D exchange in different ligation states provided structural insight into these effects. Transfection of eukaryotic cells showed that phosphorylation at sites S40 and S82 may reduce steady-levels of NQO1 protein by enhanced proteasome-induced degradation. We show that site-specific phosphorylation of human NQO1 may cause pleiotropic and counterintuitive effects on this multifunctional protein with potential implications for its relationships with human disease. Our approach allows to establish relationships between site-specific phosphorylation, functional and structural stability effects in vitro and inside cells paving the way for more detailed analyses of phosphorylation at the flavoproteome scale.

关键词： Flavoprotein Phosphorylation structure-function relationships

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：