Structural Bioinformatics and Big Data Analytics: A mini-review

Structural Biology and Structural Bioinformatics are two complementary areas that deal with three dimensional structures of biomolecules. With the advent of high-throughput techniques and automation of identifying structures there is a barrage of data generated currently, which fall under the area of Big Data. In this review, we present examples and current approach to handle massive volume of structural data and some potential applications of Big Data from Structural Bioinformatics perspective.

Thermostability in endoglucanases is fold-specific

<p>Abstract</p> <p>Background</p> <p>Endoglucanases are usually considered to be synergistically involved in the initial stages of cellulose breakdown-an essential step in the bioprocessing of lignocellulosic plant materials into bioethanol. Despite their economic importance, we currently lack a basic understanding of how some endoglucanases can sustain their ability to function at elevated temperatures required for bioprocessing, while others cannot. In this study, we present a detailed comparative analysis of both thermophilic and mesophilic endoglucanases in order to gain insights into origins of thermostability. We analyzed the sequences and structures for sets of endoglucanase proteins drawn from the Carbohydrate-Active enZymes (CAZy) database.</p> <p>Results</p> <p>Our results demonstrate that thermophilic endoglucanases and their mesophilic counterparts differ significantly in their amino acid compositions. Strikingly, these compositional differences are specific to protein folds and enzyme families, and lead to differences in intramolecular interactions in a fold-dependent fashion.</p> <p>Conclusions</p> <p>Here, we provide fold-specific guidelines to control thermostability in endoglucanases that will aid in making production of biofuels from plant biomass more efficient.</p

Structural Characterization of CalS8, a TDP-α-D-Glucose Dehydrogenase Involved in Calicheamicin Aminodideoxypentose Biosynthesis

Classical UDP-glucose 6-dehydrogenases (UGDHs; EC 1.1.1.22) catalyze the conversion of UDP-α-d-glucose (UDP-Glc) to the key metabolic precursor UDP-α-d-glucuronic acid (UDP-GlcA) and display specificity for UDP-Glc. The fundamental biochemical and structural study of the UGDH homolog CalS8 encoded by the calicheamicin biosynthetic gene is reported and represents one of the first studies of a UGDH homolog involved in secondary metabolism. The corresponding biochemical characterization of CalS8 reveals CalS8 as one of the first characterized base-permissive UGDH homologs with a \u3e15-fold preference for TDP-Glc over UDP-Glc. The corresponding structure elucidations of apo-CalS8 and the CalS8·substrate·cofactor ternary complex (at 2.47 and 1.95 Å resolution, respectively) highlight a notably high degree of conservation between CalS8 and classical UGDHs where structural divergence within the intersubunit loop structure likely contributes to the CalS8 base permissivity. As such, this study begins to provide a putative blueprint for base specificity among sugar nucleotide-dependent dehydrogenases and, in conjunction with prior studies on the base specificity of the calicheamicin aminopentosyltransferase CalG4, provides growing support for the calicheamicin aminopentose pathway as a TDP-sugar-dependent process

Structural Dynamics of a Methionine γ-lyase for Calicheamicin Biosynthesis: Rotation of the Conserved Tyrosine Stacking with Pyridoxal Phosphate

CalE6 from Micromonospora echinospora is a (pyridoxal 5′ phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acidcomplex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structuralanalysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation

Application of Molecular Simulations Toward Understanding Cellulase Mechanisms

Computational approaches have provided new biological insights into the chemical mechanism of action of cellulases, which are used in the industrial production of bioethanol. Fine-grained methods, such as molecular dynamics and quantum mechanics, as well as coarse-grained methods, such as elastic network models, were used to investigate how the chemistry and structural dynamics of these enzymes contribute to their function. In this review, we highlight recent computational studies to understand this crucial biofuel enzyme class’s chemistry and structural dynamics, as well as their significance in revealing enzymatic mechanism of action. Computational methods can complement and amplify the findings of experimental methods, which can be used in tandem to create more efficient industrial enzymes

A clade-specific Arabidopsis gene connects primary metabolism and senescence

Nearly immobile, plants have evolved new components to be able to respond to changing environments. One example is Qua Quine Starch (QQS, AT3G30720), an Arabidopsis thaliana-specific orphan gene that integrates primary metabolism with adaptation to environment changes. SAQR (Senescence-Associated and QQS-Related, AT1G64360), is unique to a clade within the family Brassicaceae; as such, the gene may have arisen about 20 million years ago. SAQR is up-regulated in QQS RNAi mutants and in the apx1 mutant under light-induced oxidative stress. SAQR plays a role in carbon allocation: overexpression lines of SAQR have significantly decreased starch content; conversely, in a SAQR T-DNA knockout line, starch accumulation is increased. Meta-analysis of public microarray data indicates that SAQR expression is correlated with expression of a subset of genes involved in senescence, defense, and stress responses. SAQR promoter::GUS expression analysis reveals that SAQR expression increases after leaf expansion and photosynthetic capacity have peaked, just prior to visible natural senescence. SAQR is expressed predominantly within leaf and cotyledon vasculature, increasing in intensity as natural senescence continues, and then decreasing prior to death. In contrast, under experimentally-induced senescence, SAQR expression increases in vasculature of cotyledons but not in true leaves. In SAQR knockout line, the transcript level of the dirigent-like disease resistance gene (AT1G22900) is increased, while that of the Early Light Induced Protein 1 gene (ELIP1, AT3G22840) is decreased. Taken together, these data indicate that SAQR may function in the QQS network, playing a role in integration of primary metabolism with adaptation to internal and environmental changes, specifically those that affect the process of senescence