scholarly journals Cis-nonPro Peptides: Genuine Occurrences and their Functional Roles

2018 ◽  
Author(s):  
Christopher J. Williams ◽  
Lizbeth L. Videau ◽  
David C. Richardson ◽  
Jane S. Richardson
Keyword(s):  
Disulfide Bonds ◽  
Active Sites ◽  
Protein Structures ◽  
The Other ◽  
Functional Roles ◽  
High Incidence ◽  
Tim Barrel ◽  
Quality Filtering ◽  
Carbohydrate Enzymes ◽  
Stringent Quality

AbstractCis-nonPro peptides, a very rare feature in protein structures, are of considerable importance for two opposite reasons. On one hand, their genuine occurrences are mostly found at sites critical to biological function, from the active sites of carbohydrate enzymes to rare adjacent-residue disulfide bonds. On the other hand, a cis-nonPro can easily be misfit into weak or ambiguous electron density, which has led to a high incidence of unjustified cis-nonPro over the last decade. This paper uses the greatly expanded crystallographic data and newly stringent quality-filtering to identify the genuine occurrences and survey both individual examples and broad patterns of their functionality. The accompanying paper describes the problem of cis-nonPro over-use, including its causes, validation, and correction.We explain the procedure developed to identify genuine cis-nonPro examples with almost no false positives, including the new observation that peptides with a glycine on one side or the other need extra care to avoid mis-assignment as cis-nonPro. We then survey a sample of the varied functional roles and structural contexts of cis-nonPro, emphasizing aspects not previously covered systematically: the preferred occurrence at β-strand ends in TIM barrel structures, the concentration of occurrence in proteins that process, bind, or contain carbohydrates, and the resulting complications in defining a simple occurrence frequency.

scholarly journals Metals in Calluna vulgaris, Empetrum nigrum, Festuca vivipara and Thymus praecox ssp. arcticus in the geothermal areas of Iceland

2021 ◽  
Author(s):  
Adam Rajsz ◽  
Bronisław Wojtuń ◽  
Aleksandra Samecka-Cymerman ◽  
Paweł Wąsowicz ◽  
Lucyna Mróz ◽  
...  
Keyword(s):  
Active Sites ◽  
Calluna Vulgaris ◽  
Bioaccumulation Factor ◽  
The Other ◽  
Extreme Situation ◽  
Empetrum Nigrum ◽  
Geothermal Activity ◽  
High Concentrations ◽  
And Control ◽  
Festuca Vivipara

AbstractThis investigation was conducted to identify the content of metals in Calluna vulgaris (family Ericaceae), Empetrum nigrum (family Ericaceae), Festuca vivipara (family Poaceae) and Thymus praecox subsp. arcticus (family Lamiaceae), as well as in the soils where they were growing in eight geothermal heathlands in Iceland. Investigation into the vegetation of geothermal areas is crucial and may contribute to their proper protection in the future and bring more understanding under what conditions the plants respond to an ecologically more extreme situation. Plants from geothermally active sites were enriched with metals as compared to the same species from non-geothermal control sites (at an average from about 150 m from geothermal activity). The enriched metals consisted of Cd, Co, Cu, Fe and Ni in C. vulgaris; Cd, Mn and Ti in E. nigrum; Hg and Pb in F. vivipara; and Cd, Fe and Hg in T. praecox. Notably, C. vulgaris, E. nigrum, F. vivipara and T. praecox had remarkably high concentrations of Ti at levels typical of toxicity thresholds. Cd and Pb (except for C. vulgaris and F. vivipara) were not accumulated in the shoots of geothermal plants. C. vulgaris from geothermal and control sites was characterised by the highest bioaccumulation factor (BF) of Ti and Mn; E. nigrum and F. vivipara by the highest BF of Ti and Cr; and T. praecox by the highest BF of Ti and Zn compared to the other elements. In comparison with the other examined species, F. vivipara from geothermal sites had the highest concentration of Ti in above-ground parts at any concentration of plant-available Ti in soil.

Relative Distribution and Incidence of Viruses Associated with Disease Outbreaks in Tomato Fields in Trinidad

2006 ◽  
Vol 7 (1) ◽  
pp. 29
Author(s):  
S. N. Rampersad
Keyword(s):  
Production Systems ◽  
Management Strategies ◽  
Disease Outbreaks ◽  
Tobacco Etch Virus ◽  
The Other ◽  
Multiple Infections ◽  
Relative Distribution ◽  
Tomato Production ◽  
Viral Pathogen ◽  
High Incidence

Tomato production in Trinidad has suffered considerable losses in yield and fruit quality due to infections of hitherto surmised etiology. In order to develop strategies for controlling viral diseases in tomato, the relative distribution and incidence of seven viruses that commonly infect tomato were determined. Of the 362 samples tested, Potato yellow mosaic Trinidad virus (PYMTV) was found in every farm except two and was present at relatively high incidence throughout the country. Tobacco mosaic virus (TMV) and Tobacco etch virus (TEV) were found in fewer farms and at lower incidences while the other viruses were absent. Single infections of either virus were more common than double infections and multiple infections were rare but present. The results indicated that PYMTV is the predominant and most important viral pathogen in tomato production systems in Trinidad; however, begomovirus disease management strategies will also have to accommodate controls Accepted for publication 10 January 2006. Published 9 March 2006.

scholarly journals Involvement of loop 5 lysine residues and the N-terminal β-hairpin of the ribotoxin hirsutellin A on its insecticidal activity

2016 ◽  
Vol 397 (2) ◽  
pp. 135-145 ◽  
Author(s):  
Miriam Olombrada ◽  
Lucía García-Ortega ◽  
Javier Lacadena ◽  
Mercedes Oñaderra ◽  
José G. Gavilanes ◽  
...  
Keyword(s):  
Active Sites ◽  
Structural Changes ◽  
The Other ◽  
Spatial Proximity ◽  
Ribonucleolytic Activity ◽  
The Family ◽  
Lysine Residues ◽  
Hirsutella Thompsonii ◽  
Close Spatial Proximity ◽  
High Degree

Abstract Ribotoxins are cytotoxic members of the family of fungal extracellular ribonucleases best represented by RNase T1. They share a high degree of sequence identity and a common structural fold, including the geometric arrangement of their active sites. However, ribotoxins are larger, with a well-defined N-terminal β-hairpin, and display longer and positively charged unstructured loops. These structural differences account for their cytotoxic properties. Unexpectedly, the discovery of hirsutellin A (HtA), a ribotoxin produced by the invertebrate pathogen Hirsutella thompsonii, showed how it was possible to accommodate these features into a shorter amino acid sequence. Examination of HtA N-terminal β-hairpin reveals differences in terms of length, charge, and spatial distribution. Consequently, four different HtA mutants were prepared and characterized. One of them was the result of deleting this hairpin [Δ(8-15)] while the other three affected single Lys residues in its close spatial proximity (K115E, K118E, and K123E). The results obtained support the general conclusion that HtA active site would show a high degree of plasticity, being able to accommodate electrostatic and structural changes not suitable for the other previously known larger ribotoxins, as the variants described here only presented small differences in terms of ribonucleolytic activity and cytotoxicity against cultured insect cells.

How “Native” Are Heritage Speakers?

2013 ◽  
Vol 10 (2) ◽  
pp. 153-177 ◽  
Author(s):  
Silvina Montrul
Keyword(s):  
Language Learning ◽  
Experimental Evidence ◽  
Native Speakers ◽  
Learning Experience ◽  
Age Of Acquisition ◽  
The Other ◽  
Gender Agreement ◽  
Heritage Speakers ◽  
High Incidence ◽  
Incomplete Acquisition

One of the chief characteristics of heritage speakers is that they range in proficiency from “overhearers” to “native” speakers. To date, the vast majority of linguistic and psycholinguistic studies have characterized the non-target-like linguistic abilities of heritage speakers as a product of incomplete acquisition and/or attrition due to reduced exposure and opportunities to use the language during childhood. This article focuses on the other side of the problem, emphasizing instead the high incidence of native-like abilities in adult heritage speakers. I illustrate this issue with recent experimental evidence from gender agreement in Spanish, a grammatical feature that is mastered at almost 100% accuracy in production by native speakers;yet it is one of the most difficult areas to master for non-native speakers, including near-natives.I discuss how age of acquisition and language-learning experience explain these effects.

Pharmacogenetics: Its Place in Medicine and Biology

1992 ◽  
Vol 5 (6) ◽  
pp. 312-316 ◽  
Author(s):  
Werner Kalow
Keyword(s):  
Infectious Disease ◽  
Drug Toxicity ◽  
Rare Variants ◽  
The Other ◽  
New Drugs ◽  
Case Histories ◽  
High Incidence ◽  
New Knowledge ◽  
Toxic Exposures ◽  
Technical Advances

A young science serves its purpose if it leads not only to new knowledge, but to new insights and concepts. This article opens with examples to illustrate some former thinking that the introduction of pharmacogenetic has overcome. Pharmacogenetic case histories from discovery to the present illustrate the interlocking of observations, technical advances, and changing concepts. There are striking biological similarities between pharmacogenetics and those inborn factors that cause resistance to infectious disease: Both represent person-to-person variations that may help the survival of populations, one when facing massive toxic exposures, the other when facing plagues and epidemics. Thus pharmacogenetics represents a biologically necessary variability of the defenses against chemical intruders, and this includes drugs. While this variability is desirable, drug toxicity occurring on the basis of this variability must be avoided. The most successful defendants against toxicity due to polymorphic (ie, high incidence) variants should be the designers of new drugs. The only defender concerned with rare variants can be the attentive clinician.

scholarly journals Comprehensive elucidation of the structural and functional roles of engineered disulfide bonds in antibody Fc fragment

2018 ◽  
Vol 293 (49) ◽  
pp. 19127-19135 ◽  
Author(s):  
Fang Zeng ◽  
Chunpeng Yang ◽  
Xinyu Gao ◽  
Xuan Li ◽  
Zhe Zhang ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Fc Fragment ◽  
Functional Roles

scholarly journals Identification of protein pockets and cavities by Euclidean Distance Transform

2018 ◽  
Author(s):  
Sebastian Daberdaku
Keyword(s):  
Ligand Binding ◽  
Active Sites ◽  
Euclidean Distance ◽  
Protein Structures ◽  
Ligand Docking ◽  
Distance Transform ◽  
Structure Based Drug Design ◽  
Distance Map ◽  
Euclidean Distance Transform ◽  
Protein Pockets

Protein pockets and cavities usually coincide with the active sites of biological processes, and their identification is significant since it constitutes an important step for structure-based drug design and protein-ligand docking applications. This paper presents a novel purely geometric algorithm for the detection of ligand binding protein pockets and cavities based on the Euclidean Distance Transform (EDT). The EDT can be used to compute the Solvent-Excluded surface for any given probe sphere radius value at high resolutions and in a timely manner. The algorithm is adaptive to the specific candidate ligand: it computes two voxelised protein surfaces using two different probe sphere radii depending on the shape of the candidate ligand. The pocket regions consist of the voxels located between the two surfaces, which exhibit a certain minimum depth value from the outer surface. The distance map values computed by the EDT algorithm during the second surface computation can be used to elegantly determine the depth of each candidate pocket and to rank them accordingly. Cavities on the other hand, are identified by scanning the inside of the protein for voids. The algorithm determines and outputs the best k candidate pockets and cavities, i.e. the ones that are more likely to bind to the given ligand. The method was applied to a representative set of protein-ligand complexes and their corresponding unbound protein structures to evaluate its ligand binding site prediction capabilities, and was shown to outperform most of the previously developed purely geometric pocket and cavity search methods.

scholarly journals Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix

2020 ◽  
Vol 76 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Nigel W. Moriarty ◽  
Pawel A. Janowski ◽  
Jason M. Swails ◽  
Hai Nguyen ◽  
Jane S. Richardson ◽  
...  
Keyword(s):  
Force Field ◽  
Active Sites ◽  
Protein Structures ◽  
Target Function ◽  
Real Space ◽  
Model Quality ◽  
Nonbonded Interactions ◽  
Amber Force Field ◽  
Quantum Mechanical Representation ◽  
Improved Model

The refinement of biomolecular crystallographic models relies on geometric restraints to help to address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here, an integration of the full all-atom Amber molecular-dynamics force field into Phenix crystallographic refinement is presented, which enables more complete modeling of biomolecular chemistry. The advantages of the force field include a carefully derived set of torsion-angle potentials, an extensive and flexible set of atom types, Lennard–Jones treatment of nonbonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over 22 000 protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better, clashscores and MolProbity scores are significantly improved, and the modeling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined using traditional geometry restraints. In general it is found that model improvements are greatest at lower resolutions, prompting plans to add the Amber target function to real-space refinement for use in electron cryo-microscopy. This work opens the door to the future development of more advanced applications such as Amber-based ensemble refinement, quantum-mechanical representation of active sites and improved geometric restraints for simulated annealing.

scholarly journals Structural Modeling and Analysis of Pregnancy-Associated Glycoprotein-1 of Buffalo (Bubalus bubalis)

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jerome Andonissamy ◽  
S. K. Singh ◽  
S. K. Agarwal
Keyword(s):  
Protein Structure ◽  
Active Sites ◽  
Structural Model ◽  
Protein Structures ◽  
Structural Modeling ◽  
Bubalus Bubalis ◽  
High Energy ◽  
Docking Studies ◽  
Modeling And Analysis ◽  
Structural Conformity

The present study was conducted to design and analyze the structural model of buffalo pregnancy-associated glycoprotein-1 (PAG-1) using bioinformatics. Structural modeling of the deduced buffalo PAG-1 protein was done using PHYRE, CONSURF servers and its structure was subsequently constructed using MODELLER 9.9 and PyMOL softwares Buffalo PAG-1 structural conformity was analyzed using PROSA, WHATIF, and 3D-PSSM servers. Designed buffalo PAG-1 protein structure on BLAST analysis retrieved protein structures belonging to aspartic proteinase family. Moreover in silico analysis revealed buffalo PAG-1 protein retained bilobed structure with pepstatin-binding clefts near the active sites by docking studies with pepstatin A using PatchDock server. Structural studies revealed that the amino and carboxy terminal containing aspartic residues are highly conserved and buried within the protein structure. Structural conformity studies showed that more than 90% of the residues lie inside favored and allowed regions. It was also deduced that buffalo PAG-1 possesses low and high energy zones with a very low threshold for proteolysis ascertaining the stableness of the buffalo PAG-1 protein structure. This study depicts the structural conformity and stability of buffalo PAG-1 protein.

scholarly journals VENOUS CONDUITS IN CORONARY SURGERY: OLD PROBLEMS — NEW SOLUTIONS

2019 ◽  
Vol 34 (1) ◽  
pp. 24-32
Author(s):  
Y. Y. Vecherskiy ◽  
D. V. Manvelyan ◽  
V. V. Zatolokin ◽  
V. M. Shipulin
Keyword(s):  
Coronary Artery ◽  
Soft Tissues ◽  
The Other ◽  
Wound Complications ◽  
Coronary Surgery ◽  
Surgical Revascularization ◽  
Other Hand ◽  
Venous Shunt ◽  
High Incidence

The introduction of autovenous coronary artery bypass grafting (CABG) marked the era of surgical revascularization in patients with coronary artery disease. It provided effective treatment for angina and significantly improved the long-term prognosis. Venous transplants today remain the most popular conduits in coronary surgery due to their availability, ease of harvesting, and the absence of length restrictions. Despite the advantages of autovenous CABG, the main disadvantage is the high incidence of venous graft failure, which represents an important and unresolved problem in cardiac and cardiovascular surgery. On the other hand, the traditional allocation of a large saphenous vein implies the dissection of soft tissues throughout the length of the isolated conduit. Traumatic dissection causes a long-lasting persistent pain syndrome after surgery, frequent abnormalities in  skin sensitivity, and a high incidence of wound complications in the lower extremities. These complications lengthen the period of rehabilitation of patients and worsen the quality of life. There is an approach of isolating the vein in a block with surrounding tissues to optimize the long-term functioning of the venous shunt, however, this technique is even more traumatic than the traditional method, and therefore its use is limited in practice. On the other hand, the introduction of minimally invasive methods of isolation allowed to reduce the incidence of wound complications and to improve the cosmetic result, but there is no convincing data regarding the effect on the consistency of shunts in the long-term postoperative period. The problems associated with the use of venous conduits in CABG are multifaceted, and their solutions are necessary to improve the effectiveness of surgical revascularization.

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