Structural studies of Cba3 and biochemical studies of human Orc6

2013 ◽  
Author(s):  
Li Xing
Keyword(s):  
Structural Studies ◽  
Biochemical Studies

scholarly journals Importance of Zika Virus NS5 Protein for Viral Replication

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 169 ◽  
Author(s):  
Hesham Elshahawi ◽  
Sharifah Syed Hassan ◽  
Vinod Balasubramaniam
Keyword(s):  
Viral Replication ◽  
Zika Virus ◽  
Drug Repurposing ◽  
French Polynesia ◽  
Innate Immune ◽  
Structural Studies ◽  
Rna Dependent Rna Polymerase ◽  
Biochemical Studies ◽  
Major Outbreak ◽  
Virus Survival

Zika virus is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. A few mild cases were recorded between 1960 and 1980 until the first major outbreak in 2007 on Yap Island. This was followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015), which significantly increased both Guillain-Barre syndrome and microcephaly cases. No current vaccines or treatments are available, however, recent studies have taken interest in the NS5 protein which encodes both the viral methyltransferase and RNA-dependent RNA polymerase. This makes it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors, while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them might inhibit or abolish the viral infection. Drug repurposing targeting the NS5 protein has also proven to be an effective tool since hundreds of thousands of compounds can be screened therefore saving time and resources, moreover information on these compounds might already be available especially if they are used to treat other ailments.

scholarly journals Structural studies reveal flexible roof of active site responsible for ω-transaminase CrmG overcoming by-product inhibition

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jinxin Xu ◽  
Xiaowen Tang ◽  
Yiguang Zhu ◽  
Zhijun Yu ◽  
Kai Su ◽  
...  
Keyword(s):  
Pharmaceutical Industry ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Product Inhibition ◽  
Strong Interactions ◽  
Structural Studies ◽  
Biochemical Studies ◽  
Fundamental Challenge ◽  
Amine Compounds

AbstractAmine compounds biosynthesis using ω-transaminases has received considerable attention in the pharmaceutical industry. However, the application of ω-transaminases was hampered by the fundamental challenge of severe by-product inhibition. Here, we report that ω-transaminase CrmG from Actinoalloteichus cyanogriseus WH1-2216-6 is insensitive to inhibition from by-product α-ketoglutarate or pyruvate. Combined with structural and QM/MM studies, we establish the detailed catalytic mechanism for CrmG. Our structural and biochemical studies reveal that the roof of the active site in PMP-bound CrmG is flexible, which will facilitate the PMP or by-product to dissociate from PMP-bound CrmG. Our results also show that amino acceptor caerulomycin M (CRM M), but not α-ketoglutarate or pyruvate, can form strong interactions with the roof of the active site in PMP-bound CrmG. Based on our results, we propose that the flexible roof of the active site in PMP-bound CrmG may facilitate CrmG to overcome inhibition from the by-product.

scholarly journals Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhiming Wang ◽  
Jeremy Rahkola ◽  
Jasmina S. Redzic ◽  
Ying-Chih Chi ◽  
Norman Tran ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Active Site ◽  
Substrate Recognition ◽  
General Strategy ◽  
Structural Studies ◽  
Opportunistic Pathogens ◽  
Cryo Electron Microscopy ◽  
Iga1 Protease ◽  
Biochemical Studies ◽  
Monoclonal Antibody Binding

AbstractOpportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since their discovery nearly 30 years ago despite the potential for developing vaccines that target these enzymes to block infection. Here we show through a series of cryo-electron microscopy single particle reconstructions how the Streptococcus pneumoniae IgA1 protease facilitates IgA1 substrate recognition and how this can be inhibited. Specifically, the Streptococcus pneumoniae IgA1 protease subscribes to an active-site-gated mechanism where a domain undergoes a 10.0 Å movement to facilitate cleavage. Monoclonal antibody binding inhibits this conformational change, providing a direct means to block infection at the host interface. These structural studies explain decades of biological and biochemical studies and provides a general strategy to block Streptococcus pneumoniae IgA1 protease activity to potentially prevent infection.

scholarly journals Importance of NS5 Protein for Zika Virus Survival

2019 ◽  
Author(s):  
Hesham Elshahawi ◽  
Sharifah Syed Hassan ◽  
Vinod Balasubramaniam
Keyword(s):  
Drug Repurposing ◽  
Fold Increase ◽  
French Polynesia ◽  
Innate Immune ◽  
Mosquito Vector ◽  
Structural Studies ◽  
Aedes Mosquito ◽  
Biochemical Studies ◽  
Major Outbreak ◽  
Virus Survival

ZIKV is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. 14 mild cases were recorded between 1960 and 1980 until the first major outbreak was recorded in 2007 on Yap island followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015) leading to a 20-fold increase in GBS and Microcephaly cases respectively. Various transmission methods have been recorded ranging from Aedes mosquito vector transmission to sexual and vertical transmission. No current vaccines or treatments are available but recent studies have taken interest in the NS5 protein which has both the RdRp & MTase domains making it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them can inhibit or abolish the viral infection. Drug repurposing has proven to be an effective tool since hundreds of thousands of compounds can be screened in-silico thus saving time and resources while also having information available on such compounds especially if they are already used to treat other ailments.

scholarly journals Structural and biochemical studies of an NB-ARC domain from a plant NLR immune receptor

2019 ◽  
Author(s):  
John FC Steele ◽  
Richard K Hughes ◽  
Mark J Banfield
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Protein Expression ◽  
Soluble Protein ◽  
Insect Cells ◽  
Molecular Switch ◽  
Structural Studies ◽  
Immune Receptor ◽  
Biochemical Studies ◽  
Insight Into

AbstractPlant NLRs are modular immune receptors that trigger rapid cell death in response to attempted infection by pathogens. A highly conserved nucleotide-binding domain shared with APAF-1, various R-proteins and CED-4 (NB-ARC domain) is proposed to act as a molecular switch, cycling between ADP (repressed) and ATP (active) bound forms. Studies of plant NLR NB-ARC domains have revealed functional similarities to mammalian homologues, and provided insight into potential mechanisms of regulation. However, further advances have been limited by difficulties in obtaining sufficient yields of protein suitable for structural and biochemical techniques. From protein expression screens in Escherichia coli and Sf9 insect cells, we defined suitable conditions to produce the NB-ARC domain from the tomato NLR NRC1. Biophysical analyses of this domain showed it is a folded, soluble protein. Structural studies revealed the NRC1 NB-ARC domain had co-purified with ADP, and confirmed predicted structural similarities between plant NLR NB-ARC domains and their mammalian homologues.

scholarly journals Structure of Aspergillus aculeatus β-1,4-galactanase in complex with galactobiose

2019 ◽  
Vol 75 (6) ◽  
pp. 399-404 ◽  
Author(s):  
Søs Torpenholt ◽  
Jens-Christian N. Poulsen ◽  
Sebastian Jannick Muderspach ◽  
Leonardo De Maria ◽  
Leila Lo Leggio
Keyword(s):  
Ligand Binding ◽  
Glycoside Hydrolases ◽  
Structural Studies ◽  
Aspergillus Aculeatus ◽  
The Family ◽  
Biochemical Studies

β-1,4-Galactanases are glycoside hydrolases that are involved in the degradation of pectin and belong to family 53 in the classification of glycoside hydrolases. Previous studies have elucidated the structures of several fungal and two bacterial galactanases, while biochemical studies have indicated differences in the product profiles of different members of the family. Structural studies of ligand complexes have to date been limited to the bacterial members of the family. Here, the first structure of a fungal galactanase in complex with a disaccharide is presented. Galactobiose binds to subsites −1 and −2, thus improving our understanding of ligand binding to galactanases.

scholarly journals 7-Methylguanosine Modifications in tRNA

2018 ◽  
Author(s):  
Chie Tomikawa
Keyword(s):  
Reaction Mechanism ◽  
Catalytic Mechanism ◽  
Variable Region ◽  
Modified Nucleosides ◽  
Structural Studies ◽  
Trna Modifications ◽  
The Past ◽  
Methyl Transfer ◽  
Trna Structure ◽  
Biochemical Studies

More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m7G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m7G modification occurs at position 46 in the variable region and is a product of tRNA (m7G46) methyltransferase. The m7G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. Recently, we have proposed a reaction mechanism for eubacterial tRNA m7G methyltransferase (TrmB) based on the results of biochemical studies and previous biochemical, bioinformatic, and structural studies by others. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m7G46 in tRNA have started to be determined over the past decade. To be able to better respond to diseases and infections in which the m7G modification is considered to be involved, it is still necessary to further understand the catalytic mechanism of AdoMet and/or the tRNA bound form of m7G methyltransferases. In this review, information of tRNA m7G modifications and tRNA m7G methyltransferases are summarized and the differences in reaction mechanism between tRNA m7G methyltransferase and rRNA or mRNA m7G methylation enzyme are discussed.

scholarly journals Importance of NS5 Protein to Zika Virus Survival

2019 ◽  
Author(s):  
Hesham Elshahawi ◽  
Sharifah Syed Hassan ◽  
Vinod Balasubramaniam
Keyword(s):  
Drug Repurposing ◽  
Fold Increase ◽  
French Polynesia ◽  
Innate Immune ◽  
Mosquito Vector ◽  
Structural Studies ◽  
Aedes Mosquito ◽  
Biochemical Studies ◽  
Major Outbreak ◽  
Virus Survival

ZIKV is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. 14 mild cases were recorded between 1960 and 1980 until the first major outbreak was recorded in 2007 on Yap island followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015) leading to a 20-fold increase in GBS and Microcephaly cases respectively. Various transmission methods have been recorded ranging from Aedes mosquito vector transmission to sexual and vertical transmission. No current vaccines or treatments are available but recent studies have taken interest in the NS5 protein which has both the RdRp & MTase domains making it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them can inhibit or abolish the viral infection. Drug repurposing has proven to be an effective tool since hundreds of thousands of compounds can be screened in-silico thus saving time and resources while also having information available on such compounds especially if they are already used to treat other ailments.

Ribosome Structural Organization

1974 ◽  
Vol 32 ◽  
pp. 332-333
Author(s):  
James A. Lake
Keyword(s):  
Ribosomal Proteins ◽  
Structural Organization ◽  
Three Dimensional ◽  
Small Subunit ◽  
Structural Studies ◽  
X Ray Diffraction ◽  
Specific Antibodies ◽  
X Ray ◽  
E Coli ◽  
Complete Sequences

The understanding of ribosome structure has advanced considerably in the last several years. Biochemists have characterized the constituent proteins and rRNA's of ribosomes. Complete sequences have been determined for some ribosomal proteins and specific antibodies have been prepared against all E. coli small subunit proteins. In addition, a number of naturally occuring systems of three dimensional ribosome crystals which are suitable for structural studies have been observed in eukaryotes. Although the crystals are, in general, too small for X-ray diffraction, their size is ideal for electron microscopy.

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