Structural studies on bio-active compounds. Part 11. Molecular modelling, crystallographic, and biochemical studies of the interactions of (±)-α-vinylserine with the enzyme serine hydroxymethyltransferase

1989 ◽  
pp. 431-436 ◽  
Author(s):  
Saul J. B. Tendler ◽  
Carl H. Schwalbe ◽  
Michael D. Threadgill ◽  
Michael J. Tisdale ◽  
LaVerne Schirch
Keyword(s):  
Molecular Modelling ◽  
Serine Hydroxymethyltransferase ◽  
Structural Studies ◽  
Active Compounds ◽  
Biochemical Studies

scholarly journals Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity

Molecules ◽  
2015 ◽  
Vol 20 (8) ◽  
pp. 14761-14776 ◽  
Author(s):  
Tomasz Wróbel ◽  
Urszula Kosikowska ◽  
Agnieszka Kaczor ◽  
Sylwia Andrzejczuk ◽  
Zbigniew Karczmarzyk ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Molecular Modelling ◽  
Structural Studies ◽  
Imidazoline Derivative

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.

Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP102 : structural studies on specific CYP2D6substrate metabolism

Xenobiotica ◽  
1997 ◽  
Vol 27 (4) ◽  
pp. 319-340 ◽  
Author(s):  
D. F. V. LEWIS ◽  
P. J. EDDERSHAW ◽  
P. S. GOLDFARB ◽  
M. H. TARBIT
Keyword(s):  
Molecular Modelling ◽  
Structural Studies
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