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E Srinivasan, R Rajasekaran
Amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disorder is characterized by the degeneration of upper and lower motor neuron. ALS occurs due to various notably prominent missense mutations, in gene encoding Cu-Zn superoxide dismutase (SOD1) thereby leading to aggregation, dysfunction and reduced Zn binding affinity. In this study, one such mutation, G85R was explored in comparison with wild type SOD1, using discrete molecular dynamics (DMD). Accordingly, the conformational changes were significantly observed in mutant SOD1, through various geometrical parameters, which substantiated the difference in conformational deviation, flexibility and compactness, thus stipulating a root cause for aggregation...
March 21, 2017: Proteins
Kajwal Kumar Patra, Akash Bhattacharya, Swati Bhattacharya
The human sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a retroviral restriction factor in myeloid cells and non-cycling CD4+ T cells, a feature imputed to its phosphohydrolase activity - the enzyme depletes the cellular dNTP levels inhibiting reverse transcription. The functionally active form of SAMHD1 is an allosterically triggered tetramer which utilizes GTP-Mg(+2) -dNTP cross bridges to link and stabilize adjacent monomers. However, very little is known about how it assembles into a tetramer and how long the tetramer stays intact...
March 21, 2017: Proteins
Alexandra Plácido, Andreia Coelho, Lucas Abreu do Nascimento, Andreanne Gomes Vasconcelos, Maria Fátima Barroso, Joilson Ramos-Jesus, Vladimir Costa, Francisco das Chagas Alves Lima, Cristina Delerue-Matos, Ricardo Martins Ramos, Mariela M Marani, José Roberto de Souza de Almeida Leite
Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, e.g., biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures...
March 18, 2017: Proteins
Jolanta Cieślak, Akimasa Miyanaga, Ryoma Takaku, Makoto Takaishi, Keita Amagai, Fumitaka Kudo, Tadashi Eguchi
Macrolactam antibiotics such as incednine and cremimycin possess an aliphatic β-amino acid as a starter unit of their polyketide chain. In the biosynthesis of incednine and cremimycin, unique stand-alone adenylation enzymes IdnL1 and CmiS6 select and activate the proper aliphatic β-amino acid as a starter unit. In this study, we describe the enzymatic characterization and the structural basis of substrate specificity of IdnL1 and CmiS6. Functional analysis revealed that IdnL1 and CmiS6 recognize 3-aminobutanoic acid and 3-aminononanoic acid, respectively...
March 18, 2017: Proteins
Prashasti Kumar, Engin H Serpersu
Kinetic, thermodynamic and structural properties of the aminoglycoside N3-acetyltransferase-VIa (AAC-VIa) are determined. Among the aminoglycoside N3-acetyltransferases, AAC-VIa has one of the most limited substrate profiles. Kinetic studies showed that only 5 aminoglycosides are substrates for this enzyme with a range of 4-fold difference in kcat values. Larger differences in KM (∼40 fold) resulted in ∼30-fold variation in kcat /KM . Binding of aminoglycosides to AAC-VIa was enthalpically favored and entropically disfavored with a net result of favorable Gibbs energy (ΔG<0)...
March 17, 2017: Proteins
Jin Myung Choi, Thinh-Phat Cao, Si Wouk Kim, Kun Ho Lee, Sung Haeng Lee
MxaJ is a component of type II methanol dehydrogenase (MDH) that mediates electron transfer during methanol oxidation in methanotrophic bacteria. However, little is known about how MxaJ structurally cooperates with MDH and Cytochrome cL . Here, we report for the first time the crystal structure of MxaJ. MxaJ consists of eight α-helices and six β-strands, and resembles the "bi-lobate" folding architecture found in periplasmic binding proteins. Distinctive features of MxaJ include prominent loops and a β-strand around the hinge region supporting the ligand-binding cavity, which might provide a more favorable framework for interacting with proteins rather than small molecules...
March 13, 2017: Proteins
Ayixon Sánchez-Reyez, Ramón Alberto Batista-García, Gilberto Valdés-García, Ernesto Ortiz, Lucía Perezgasga, Andrés Zárate-Romero, Nina Pastor, Jorge Luis Folch-Mallol
Activated sludge is produced during the treatment of sewage and industrial wastewaters. Its diverse chemical composition allows growth of a large collection of microbial phylotypes with very different physiologic and metabolic profiles. Thus, activated sludge is considered as an excellent environment to discover novel enzymes through functional metagenomics, especially activities related with degradation of environmental pollutants. Metagenomic DNA was isolated and purified from an activated sludge sample. Metagenomic libraries were subsequently constructed in Escherichia coli...
March 9, 2017: Proteins
Claudio Mirabello, Björn Wallner
Protein-protein interactions (PPI) are crucial for protein function. There exist many techniques to identify PPIs experimentally, but to determine the interactions in molecular detail is still difficult and very time-consuming. The fact that the number of PPIs is vastly larger than the number of individual proteins makes it practically impossible to characterize all interactions experimentally. Computational approaches that can bridge this gap and predict PPIs and model the interactions in molecular detail are greatly needed...
March 6, 2017: Proteins
Martin Kulke, Norman Geist, Wenke Friedrichs, Walter Langel
Synthetic scaffolds containing collagen (Type I) are of increasing interest for bone tissue engineering, especially for highly porous biomaterials in combination with glycosaminoglycans. In experiments the integration of heparin during the fibrillogenesis resulted in different types of collagen fibrils, but models for this aggregation on a molecular scale were only tentative. We conducted molecular dynamic simulations investigating the binding of heparin to collagen and the influence of the telopeptides during collagen aggregation...
March 6, 2017: Proteins
Bian Li, Jeffrey Mendenhall, Elizabeth Dong Nguyen, Brian E Weiner, Axel W Fischer, Jens Meiler
One of the challenging problems in computational prediction of tertiary structure of helical membrane proteins (HMPs) is the determination of rotation of α-helices around the helix normal. Incorrect prediction of rotation of α-helices around the helix normal substantially disrupts native residue-residue contacts while inducing only a relatively small effect on the overall fold. To address this problem, we previously developed a predictor for residue contact numbers (CNs), which measure the local packing density of residues within the protein tertiary structure...
March 6, 2017: Proteins
Lihua Dong, Yongjun Liu
Chorismatase is an important enzyme involved in Shikimate pathway, which catalyzes the conversion of chorismate into pyruvate and (dihydro)-benzoic acid derivatives. According to the outcomes of catalytic reactions, chorismatases can be divided into three subfamilies: CH-Fkbo, CH-Hyg5 and CH-XanB2. Recently, the crystal structures of CH-Fkbo and CH-Hyg5 from Streptomyces hygroscopicus have been successfully obtained, allowing us to perform QM/MM calculations to explore the reaction details. Our calculation results support the proposal that CH-Fkbo and CH-Hyg5 employ different catalytic mechanisms and gave the mechanistic details...
March 6, 2017: Proteins
Kliment Olechnovič, Česlovas Venclovas
In the absence of experimentally determined protein structure many biological questions can be addressed using computational structural models. However, the utility of protein structural models depends on their quality. Therefore, the estimation of the quality of predicted structures is an important problem. One of the approaches to this problem is the use of knowledge-based statistical potentials. Such methods typically rely on the statistics of distances and angles of residue-residue or atom-atom interactions collected from experimentally determined structures...
March 6, 2017: Proteins
Prabakaran Ramakrishnan, Dhruv Goel, Sandeep Kumar, M Michael Gromiha
Protein aggregation leads to several burdensome human maladies, but a molecular level understanding of how human proteome has tackled the threat of aggregation is currently lacking. In this work, we survey the human proteome for incidence of aggregation prone regions (APRs), by using sequences of experimentally validated amyloid-fibril forming peptides and via computational predictions. While approximately 30 human proteins are currently known to be amyloidogenic, we found that 260 proteins (∼1% of human proteome) contain at least one experimentally validated amyloid-fibril forming segment...
March 3, 2017: Proteins
Yipeng Cao, Xue Wu, Rui Yang, Xinyu Wang, Haiying Sun, Imshik Lee
The Sarcolipin (SLN) is a single trans-membrane protein that can self-assembly to dimer and oligomer for playing importantphysiological function. In this work, we addressed the dimerization of wild type SLN (wSLN) and its mutants (mSLNs) - I17A and I20A, using both coarse-grained (CG) and atomistic (AT) molecular dynamics (MD) simulations. Our results demonstrated that wSLN homodimer assembled as a left-handed helical complex, while mSLNs heterodimers assembled as right-handed complexes. Analysis of residue-residue contacts map indicated that isoleucine (Ile)-leucione (Leu) zipper domain played an important role in dimerization...
February 27, 2017: Proteins
George A Khoury, James Smadbeck, Chris A Kieslich, Alexandra J Koskosidis, Yannis A Guzman, Phanourios Tamamis, Christodoulos A Floudas
Protein structure refinement is the challenging problem of operating on any protein structure prediction to improve its accuracy with respect to the native structure in a blind fashion. Although many approaches have been developed and tested during the last four CASP experiments, a majority of the methods continue to degrade models rather than improve them. Princeton_TIGRESS (Khoury et al., Proteins 2014;82:794-814) was developed previously and utilizes separate sampling and selection stages involving Monte Carlo and molecular dynamics simulations and classification using an SVM predictor...
February 27, 2017: Proteins
Charles R Watts, Andrew J Gregory, Cole P Frisbie, Sándor Lovas
Replica exchange molecular dynamics simulations (300 ns) were used to study the dimerization of amyloid β(1-40) (Aβ(1-40)) polypeptide. Configurational entropy calculations revealed that at physiologic temperature (310 K, 37°C) dynamic dimers are formed by randomly docked monomers. Free energy of binding of the two chains to each other was -93.56 ± 6.341 kJ mol(-1) . Prevalence of random coil conformations was found for both chains with the exceptions of increased β-sheet content from residues 16-21 and 29-32 of chain A and residues 15-21 and 30-33 of chain B with β-turn/β-bend conformations in both chains from residues 1-16, 21-29 of chain A, 1-16, and 21-29 of chain B...
February 27, 2017: Proteins
Aysima Hacisuleyman, Burak Erman
A fast and approximate method of generating allosteric communication landscapes in proteins is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but an ensemble of pathways is possible. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations should be introduced, which leads to the presence of causality in proteins...
February 27, 2017: Proteins
Abhisek Mondal, Saumen Datta
Hydrogen bond plays a unique role in governing macromolecular interactions with exquisite specificity. These interactions govern the fundamental biological processes like protein folding, enzymatic catalysis, molecular recognition. Despite extensive research work, till date there is no proper report available about the hydrogen bond's energy surface with respect to its geometric parameters, directly derived from proteins. Herein, we have deciphered the potential energy landscape of hydrogen bond directly from the macromolecular coordinates obtained from Protein Data Bank using quantum mechanical electronic structure calculations...
February 27, 2017: Proteins
Shaogui Wu
Two magnesium ions play important roles in nucleotide addition cycle (NAC) of gene transcription. However, at the end of each NAC, why does one ion stay in the active site while the other ion leaves with product pyrophosphate (PPi )? This problem still remains obscure. In the present work, we studied the problem using all-atom molecular dynamics (MD) simulation combined with steered molecular dynamics (SMD) and umbrella sampling (US) simulation methods. Our simulations reveal that although both ions are located in the active site after chemistry, their detailed positions are not symmetrical, leading to their different forces from surrounding groups...
February 16, 2017: Proteins
Masahiko Okai, Woo Cheol Lee, Li-Jun Guan, Takashi Ohshiro, Yoshikazu Izumi, Masaru Tanokura
The dibenzothiophene (DBT) sulfone monooxygenase BdsA from Bacillus subtilis WU-S2B catalyzes the conversion of DBT sulfone to 2'-hydroxybiphenyl 2-sulfinate (HBPS). We report the crystal structures of BdsA at a resolution of 2.80 Å. BdsA exists as a homotetramer with a dimer-of-dimers configuration in the crystal, and the interaction between E288 and R296 in BdsA is important for tetramer formation. A structural comparison with homologous proteins shows that the orientation and location of the α9-α12 helices in BdsA are closer to those of the closed form than those of the open form in the EDTA monooxygenase EmoA...
February 16, 2017: Proteins
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