scholarly journals The folate-binding module ofThermus thermophiluscobalamin-dependent methionine synthase displays a distinct variation of the classical TIM barrel: a TIM barrel with a `twist'

2018 ◽  
Vol 74 (1) ◽  
pp. 41-51
Author(s):  
Kazuhiro Yamada ◽  
Markos Koutmos
Keyword(s):  
Tertiary Amine ◽  
Thermus Thermophilus ◽  
Methionine Synthase ◽  
Structural Studies ◽  
Binding Domains ◽  
Methyl Transfer ◽  
Structural Differences ◽  
Tim Barrel ◽  
Eukaryotic Organisms

Methyl transfer between methyltetrahydrofolate and corrinoid molecules is a key reaction in biology that is catalyzed by a number of enzymes in many prokaryotic and eukaryotic organisms. One classic example of such an enzyme is cobalamin-dependent methionine synthase (MS). MS is a large modular protein that utilizes an SN2-type mechanism to catalyze the chemically challenging methyl transfer from the tertiary amine (N5) of methyltetrahydrofolate to homocysteine in order to form methionine. Despite over half a century of study, many questions remain about how folate-dependent methyltransferases, and MS in particular, function. Here, the structure of the folate-binding (Fol) domain of MS fromThermus thermophilusis reported in the presence and absence of methyltetrahydrofolate. It is found that the methyltetrahydrofolate-binding environment is similar to those of previously described methyltransferases, highlighting the conserved role of this domain in binding, and perhaps activating, the methyltetrahydrofolate substrate. These structural studies further reveal a new distinct and uncharacterized topology in the C-terminal region of MS Fol domains. Furthermore, it is found that in contrast to the canonical TIM-barrel β8α8fold found in all other folate-binding domains, MS Fol domains exhibit a unique β8α7fold. It is posited that these structural differences are important for MS function.

scholarly journals Role of N501Y Mutation in SARS-CoV-2 Spike Protein Structure

2021 ◽  
Author(s):  
Urmi Roy
Keyword(s):  
Computer Simulation ◽  
Structural Changes ◽  
Spike Protein ◽  
Wild Type ◽  
Binding Domains ◽  
First Case ◽  
Mutant Variant ◽  
Structural Differences ◽  
Mutant Forms

It has been more than a year since the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found. This coronavirus has infected more than 110 million people worldwide by the end of February, 2021, and several virulent as well as more spreadable mutant forms of SARS-CoV-2 have emerged subsequently. In the latter group, three variants B.1.1.7, B.1.351, and P1 lineages, have been reported. Using computer simulation, the present paper investigates the structural differences between the wild type SARS-CoV-2 spike protein and its Asn501Tyr (N501Y) mutant variant. Time-based structural changes between the receptor binding domains of these two species are also examined. The N501Y mutation is common to all the three aforesaid mutant variants.

scholarly journals RNA Helicase A Regulates the Replication of RNA Viruses

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 361
Author(s):  
Rui-Zhu Shi ◽  
Yuan-Qing Pan ◽  
Li Xing
Keyword(s):  
Virus Replication ◽  
Rna Binding ◽  
Rna Viruses ◽  
Rna Helicase ◽  
Rna Helicase A ◽  
Double Stranded Rna ◽  
Binding Domains ◽  
N Terminus

The RNA helicase A (RHA) is a member of DExH-box helicases and characterized by two double-stranded RNA binding domains at the N-terminus. RHA unwinds double-stranded RNA in vitro and is involved in RNA metabolisms in the cell. RHA is also hijacked by a variety of RNA viruses to facilitate virus replication. Herein, this review will provide an overview of the role of RHA in the replication of RNA viruses.

scholarly journals Functional Characterization of Spliceosomal Introns and Identification of U2, U4, and U5 snRNAs in the Deep-Branching Eukaryote Entamoeba histolytica

2007 ◽  
Vol 6 (6) ◽  
pp. 940-948 ◽  
Author(s):  
Carrie A. Davis ◽  
Michael P. S. Brown ◽  
Upinder Singh
Keyword(s):  
Entamoeba Histolytica ◽  
Splice Site ◽  
Expressed Sequence Tag ◽  
Functional Characterization ◽  
Molecular Evidence ◽  
Spliceosomal Introns ◽  
Accurate Expression ◽  
Eukaryotic Organisms

ABSTRACT Pre-mRNA splicing is essential to ensure accurate expression of many genes in eukaryotic organisms. In Entamoeba histolytica, a deep-branching eukaryote, approximately 30% of the annotated genes are predicted to contain introns; however, the accuracy of these predictions has not been tested. In this study, we mined an expressed sequence tag (EST) library representing 7% of amoebic genes and found evidence supporting splicing of 60% of the testable intron predictions, the majority of which contain a GUUUGU 5′ splice site and a UAG 3′ splice site. Additionally, we identified several splice site misannotations, evidence for the existence of 30 novel introns in previously annotated genes, and identified novel genes through uncovering their spliced ESTs. Finally, we provided molecular evidence for the E. histolytica U2, U4, and U5 snRNAs. These data lay the foundation for further dissection of the role of RNA processing in E. histolytica gene expression.

scholarly journals Role of Papillomavirus E1 Initiator Dimerization in DNA Replication

2005 ◽  
Vol 79 (13) ◽  
pp. 8661-8664 ◽  
Author(s):  
Stephen Schuck ◽  
Arne Stenlund
Keyword(s):  
Dna Replication ◽  
Dna Binding ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Severe Effect ◽  
Origin Of Dna Replication ◽  
Initiation Of Dna Replication

ABSTRACT Viral initiator proteins are polypeptides that form oligomeric complexes on the origin of DNA replication (ori). These complexes carry out a multitude of functions related to initiation of DNA replication, and although many of these functions have been characterized biochemically, little is understood about how the complexes are assembled. Here we demonstrate that loss of one particular interaction, the dimerization between E1 DNA binding domains, has a severe effect on DNA replication in vivo but has surprisingly modest effects on most individual biochemical activities in vitro. We conclude that the dimer interaction is primarily required for initial recognition of ori.

Ligand modulates the conversion of DNA-bound vitamin D3 receptor (VDR) homodimers into VDR-retinoid X receptor heterodimers

1994 ◽  
Vol 14 (5) ◽  
pp. 3329-3338
Author(s):  
B Cheskis ◽  
L P Freedman
Keyword(s):  
Ligand Binding ◽  
Vitamin D3 ◽  
Hormone Receptors ◽  
Steroid Receptors ◽  
Dependent Manner ◽  
D3 Receptor ◽  
Vitamin D3 Receptor ◽  
Binding Domains

Protein dimerization facilitates cooperative, high-affinity interactions with DNA. Nuclear hormone receptors, for example, bind either as homodimers or as heterodimers with retinoid X receptors (RXR) to half-site repeats that are stabilized by protein-protein interactions mediated by residues within both the DNA- and ligand-binding domains. In vivo, ligand binding among the subfamily of steroid receptors unmasks the nuclear localization and DNA-binding domains from a complex with auxiliary factors such as the heat shock proteins. However, the role of ligand is less clear among nuclear receptors, since they are constitutively localized to the nucleus and are presumably associated with DNA in the absence of ligand. In this study, we have begun to explore the role of the ligand in vitamin D3 receptor (VDR) function by examining its effect on receptor homodimer and heterodimer formation. Our results demonstrate that VDR is a monomer in solution; VDR binding to a specific DNA element leads to the formation of a homodimeric complex through a monomeric intermediate. We find that 1,25-dihydroxyvitamin D3, the ligand for VDR, decreases the amount of the DNA-bound VDR homodimer complex. It does so by significantly decreasing the rate of conversion of DNA-bound monomer to homodimer and at the same time enhancing the dissociation of the dimeric complex. This effectively stabilizes the bound monomeric species, which in turn serves to favor the formation of a VDR-RXR heterodimer. The ligand for RXR, 9-cis retinoic acid, has the opposite effect of destabilizing the heterodimeric-DNA complex. These results may explain how a nuclear receptor can bind DNA constitutively but still act to regulate transcription in a fully hormone-dependent manner.

A FEM Frontal Impact Study of Square-Section Tubes with Different Structural Solutions for Vehicle Safety

2015 ◽  
Vol 798 ◽  
pp. 36-40
Author(s):  
Ciro Faria Maia ◽  
Guilherme Silame Maranhão Lima ◽  
Felipe Grossi L. Amorim ◽  
Evandro Queiroz Nunes Vera ◽  
Alexander Matioli Pasqual
Keyword(s):  
Cross Sections ◽  
Initial Velocity ◽  
Impact Analysis ◽  
Vehicle Safety ◽  
Impact Study ◽  
Frontal Impact ◽  
Structural Differences ◽  
Rigid Plane ◽  
Structural Solutions

The present paper presents a study of square-section tubes conditioned to a FE dynamic frontal impact analysis, considering a 10.0 m/s initial velocity against an infinitely rigid plane. A 50.0 kg punctual mass is positioned on center of the cross-sections, on the farthest side from the rigid plane and the deceleration pulse is measured along the simulations. After validating the numerical model with analytical solutions, the results are compared for four geometries with little structural differences in order to access the role of each difference on the geometry under crash situations. The results show that adding many triggers to the geometry may not be the best performance solution for crash boxes, since the geometry with few triggers achieved better values of deceleration peak than the others. In addition, the presence of holes showed to be an instability cause to the system. The structural solutions presented could be of great value for future vehicle crash box developments.

Sign in / Sign up

Export Citation Format

Share Document