Truncation of Human Squalene Synthase Yields Active, Crystallizable Protein

1998 ◽  
Vol 350 (2) ◽  
pp. 283-290 ◽  
Author(s):  
John F. Thompson ◽  
Dennis E. Danley ◽  
Stacy Mazzalupo ◽  
Patrice M. Milos ◽  
Maruja E. Lira ◽  
...  
Keyword(s):  
Squalene Synthase ◽  
Human Squalene Synthase

Discovering Peptide Inhibitors of Human Squalene Synthase Through Screening the Phage-Displayed Cyclic Peptide c7c Library

2016 ◽  
Vol 179 (4) ◽  
pp. 597-609 ◽  
Author(s):  
David Shiuan ◽  
Yue-Hao Chen ◽  
Hwan-Kang Lin ◽  
Kao-Jean Huang ◽  
Da-Fu Tai ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Peptide Inhibitors ◽  
Squalene Synthase ◽  
Human Squalene Synthase

scholarly journals Multiple Sequence Elements are Involved in the Transcriptional Regulation of the Human Squalene Synthase Gene

1997 ◽  
Vol 272 (15) ◽  
pp. 10295-10302 ◽  
Author(s):  
Guimin Guan ◽  
Pei-Hua Dai ◽  
Timothy F. Osborne ◽  
Jae B. Kim ◽  
Ishaiahu Shechter
Keyword(s):  
Transcriptional Regulation ◽  
Squalene Synthase ◽  
Multiple Sequence ◽  
Sequence Elements ◽  
Human Squalene Synthase

Exploration of Peptide Inhibitors of Human Squalene Synthase through Molecular Modeling and Phage Display Technique

2015 ◽  
Vol 178 (2) ◽  
pp. 312-323 ◽  
Author(s):  
David Shiuan ◽  
Hwan-Kang Lin ◽  
Yue-Hao Chen ◽  
Ding-Kwo Chang ◽  
Kao-Jean Huang ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Phage Display ◽  
Peptide Inhibitors ◽  
Squalene Synthase ◽  
Phage Display Technique ◽  
Human Squalene Synthase ◽  
Display Technique

Expression, Purification, and Characterization of the Human Squalene Synthase: Use of Yeast and Baculoviral Systems

1995 ◽  
Vol 316 (2) ◽  
pp. 713-723 ◽  
Author(s):  
D.A. Soltis ◽  
G. Mcmahon ◽  
S.L. Caplan ◽  
D.A. Dudas ◽  
H.A. Chamberlin ◽  
...  
Keyword(s):  
Squalene Synthase ◽  
Purification And Characterization ◽  
Human Squalene Synthase

scholarly journals Molecular Cloning and Functional Analysis of the Promoter of the Human Squalene Synthase Gene

1995 ◽  
Vol 270 (37) ◽  
pp. 21958-21965 ◽  
Author(s):  
Guimin Guan ◽  
Guojian Jiang ◽  
Rebecca L. Koch ◽  
Ishaiahu Shechter
Keyword(s):  
Functional Analysis ◽  
Molecular Cloning ◽  
Squalene Synthase ◽  
Human Squalene Synthase

scholarly journals Using Engineered Escherichia coli to Synthesize Squalene with Optimized Manipulation of Squalene Synthase and Mevalonate Pathway

2020 ◽  
Author(s):  
Chenhao Sun ◽  
Yuancheng Ding ◽  
Bingjing Cheng ◽  
Yeqing Zong
Keyword(s):  
Escherichia Coli ◽  
Selection Pressure ◽  
Mevalonate Pathway ◽  
Squalene Synthase ◽  
Farnesyl Diphosphate ◽  
Gene Circuit ◽  
Mva Pathway ◽  
Pharmaceutical Industries ◽  
Engineered Escherichia Coli ◽  
Human Squalene Synthase

AbstractSqualene is the metabolic precursor of sterols and naturally synthesized in the deep-dea shark liver and human sebum. The utilization of squalene is wide such as food, cosmetical, and pharmaceutical industries. This experiment used engineered Escherichia coli to construct the gene circuit for the biosynthesis of squalene. Human squalene synthase (hSQS) efficiently catalyzes the synthesis of squalene. Also, mevalonate (MVA) pathway would increase the yield of the precursor of squalene, farnesyl diphosphate, which then increased the yield of squalene. Meanwhile, the regulation of MVA pathway via different inducer IPTG concentrations and creation of selection pressure by antibiotics were investigated.

scholarly journals DESIGNING OF COUMARIN DERIVATIVES AS SQUALENE SYNTHASE INHIBITORS

2018 ◽  
Vol 11 (10) ◽  
pp. 200 ◽  
Author(s):  
Firoz Mv ◽  
Vishwanathan Balasubramanya Iyer ◽  
Vishal Gupta N ◽  
Gowda Dv ◽  
Gurupadayya Bm ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Research Work ◽  
Three Dimensional ◽  
Data Bank ◽  
Squalene Synthase ◽  
Dimensional Structure ◽  
Binding Property ◽  
Coumarin Derivatives ◽  
Human Squalene Synthase ◽  
Synthase Inhibitor

Objective: The importance of this research work is to design a library of novel coumarin derivatives by docking evaluation of the designed coumarin derivatives as squalene synthase inhibitor.Methods: The three-dimensional structure of designed molecules of squalene synthase inhibitors was collected from Protein Data Bank. The designed molecules were docked onto the enzymes that are squalene synthase inhibitor - 3WCM, 3WCJ, and 3Q2Z protein using SYBYL-X 2.1. Using a standard protocol, the protein was subjected to minimization and protomol generation.Results: By this method, we visualized the possible binding and also estimated the protein interactions with our intended coumarin library, using SYBYL-X 2.1 software. Into the active site of the selected enzymes, all the 20 coumarins were docked and then the docking scores revealed that the compounds possess high affinity toward the selected enzymes.Conclusion: With the help of virtual evaluation, we have elaborated a fast synthetically accessible coumarin-based compounds, and it is an advanced and original scaffold in the area of probable human squalene synthase inhibitors. Some of the developed compounds show better binding property than ligand, and in 3q2Z, the compound 5d shows better binding property than the protein. Furthermore, 6g and 6c have good binding property. In 3 WCM, the compound 6f has better property. In 3 WCJ, the compounds 6g and 6f show better binding property than the protein.

Structural insights into the catalytic mechanism of human squalene synthase

2014 ◽  
Vol 70 (2) ◽  
pp. 231-241 ◽  
Author(s):  
Chia-I Liu ◽  
Wen-Yih Jeng ◽  
Wei-Jung Chang ◽  
Min-Fang Shih ◽  
Tzu-Ping Ko ◽  
...  
Keyword(s):  
Metal Ion ◽  
Biosynthetic Pathway ◽  
Catalytic Mechanism ◽  
Intermediate Formation ◽  
Extensive Study ◽  
Squalene Synthase ◽  
Site Directed Mutagenesis ◽  
Binding Model ◽  
New Findings ◽  
Human Squalene Synthase

Squalene synthase (SQS) is a divalent metal-ion-dependent enzyme that catalyzes the two-step reductive `head-to-head' condensation of two molecules of farnesyl pyrophosphate to form squalene using presqualene diphosphate (PSPP) as an intermediate. In this paper, the structures of human SQS and its mutants in complex with several substrate analogues and intermediates coordinated with Mg2+or Mn2+are presented, which stepwise delineate the biosynthetic pathway. Extensive study of the SQS active site has identified several critical residues that are involved in binding reduced nicotinamide dinucleotide phosphate (NADPH). Based on mutagenesis data and a locally closed (JK loop-in) structure observed in thehSQS-(F288L)–PSPP complex, an NADPH-binding model is proposed for SQS. The results identified four major steps (substrate binding, condensation, intermediate formation and translocation) of the ordered sequential mechanisms involved in the `1′–1' isoprenoid biosynthetic pathway. These new findings clarify previous hypotheses based on site-directed mutagenesis and biochemical analysis.

scholarly journals Crystal Structure of Human Squalene Synthase

2000 ◽  
Vol 275 (39) ◽  
pp. 30610-30617 ◽  
Author(s):  
Jayvardhan Pandit ◽  
Dennis E. Danley ◽  
Gayle K. Schulte ◽  
Stacy Mazzalupo ◽  
Thomas A. Pauly ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Squalene Synthase ◽  
Human Squalene Synthase
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