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Enhancing Human Spermine Synthase Activity by Engineered Mutations

Zhe Zhang, Yueli Zheng, Margo Petukh, Anthony Pegg, Yoshihiko Ikeguchi, Emil Alexov, Dennis R. Livesay
2013 PLoS Computational Biology  
Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine.  ...  In contrast to these studies, here we report an artificial engineering of a more efficient SMS variant by transferring sequence information from another organism.  ...  Negative folding energy change indicates that the mutant monomers are less stable compared with Enhancing Human Spermine Synthase Activity WT monomers, while positive energy change means increasing stability  ... 
doi:10.1371/journal.pcbi.1002924 pmid:23468611 pmcid:PMC3585406 fatcat:ng444mbe4re7botnts3m7s2hvy

Defining the role of polyamines in colon carcinogenesis using mouse models

NataliaA Ignatenko, EugeneW Gerner, DavidG Besselsen
2011 Journal of Carcinogenesis  
Genetically engineered mouse (GEM) models have made a significant contribution to the characterization of colorectal cancer risk factors.  ...  Our work in this area has been primarily supported by USPHS grants from the National Cancer Institute (CA-72008, CA-95060, and CA-123065).  ...  The hearing loss in Gy mice was reversed by breeding them with CAG/SmS mice, a transgenic line that ubiquitously expresses spermine synthase under the control of a composite cytomegalovirus-IE enhancer  ... 
doi:10.4103/1477-3163.79673 pmid:21712957 pmcid:PMC3122100 fatcat:wp4m3hsbebbb5nkxunz5cfy7pe

Characterization of transgenic mice with overexpression of spermidine synthase

Chenxu Shi, Patricia A. Welsh, Suzanne Sass-Kuhn, Xiaojing Wang, Diane E. McCloskey, Anthony E. Pegg, David J. Feith
2011 Amino Acids  
A composite cytomegalovirus-immediate early gene enhancer/chicken β-actin promoter (CAG) was utilized to generate transgenic mice that overexpress human spermidine synthase (SpdS) in order to determine  ...  the impact of elevated spermidine synthase activity on murine development and physiology.  ...  Supported by National Institutes of Health grants CA-018138 (DJF) and GM-26290 (AEP).  ... 
doi:10.1007/s00726-011-1028-6 pmid:21809077 pmcid:PMC3245749 fatcat:5mygsga3mvbj3dw5wexob7jn7e

Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines

Shannon L. Nowotarski, David J. Feith, Lisa M. Shantz
2015 Cancer Growth and Metastasis  
Putrescine is converted to the higher polyamines spermidine and spermine by spermidine synthase (SpdS) and spermine synthase (SpmS), respectively.  ...  It was originally hypothesized that genetic manipulations to enhance SSAT activity would decrease tumor susceptibility by depleting the higher polyamines spermidine and spermine.  ... 
doi:10.4137/cgm.s21219 pmid:26380554 pmcid:PMC4558889 fatcat:jipjaxmrinhmrlz5timh3guhai

Spermine synthase overexpression in vivo does not increase susceptibility to DMBA/TPA skin carcinogenesis or Min-Apc intestinal tumorigenesis

Patricia A. Welsh, Suzanne Sass-Kuhn, Chethana Prakashagowda, Diane McCloskey, David Feith
2012 Cancer Biology & Therapy  
(Spm) are produced from putrescine and the aminopropyl donor dcAdoMet by sequential action of the independent enzymes spermidine synthase (SpdS) and spermine synthase (SpmS).  ...  Spermine synthase overexpression in vivo does not increase susceptibility to DMBA/TPA skin carcinogenesis or Min-Apc intestinal tumorigenesis human FAP syndrome and it has been utilized to identify genes  ... 
doi:10.4161/cbt.19241 pmid:22258329 pmcid:PMC3341213 fatcat:p47jeexybvdgpc2c67asqn4skq

Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases

Nicole LoGiudice, Linh Le, Irene Abuan, Yvette Leizorek, Sigrid Roberts
2018 Medical Sciences  
The other Food and Drug Administration (FDA) approved application for DFMO is as an active ingredient in the hair removal cream Vaniqa.  ...  Putrescine is further converted to spermidine and spermine by the sequential actions of spermidine synthase (SPDSYN) and spermine synthase (SPMSYN).  ...  ARG: arginase; ODC: ornithine decarboxylase; SPDSYN: spermidine synthase; SPMSYN: spermine synthase; ADOMETDC: S-adenosylmethionine decarboxylase; SMO: spermine oxidase; SSAT: spermidine/spermine N1-acetyltransferase  ... 
doi:10.3390/medsci6010012 pmid:29419804 pmcid:PMC5872169 fatcat:rgnz55zvgffnpafelvmvx7nlgi

Polyamines: Small Molecules Triggering Pathways in Plant Growth and Development

R. Walden, A. Cordeiro, A. F. Tiburcio
1997 Plant Physiology  
Spain (A.F.T.) ity that provides the aminopropyl moiety that is used by spermidine and spermine synthases, respectively, to convert putrescine to spermidine and spermine.  ...  In both of these studies only an increase in putrescine levels was observed, raising the issue of whether SAMDC, spermidine synthase, or spermine synthase activities are limiting in plants.  ... 
doi:10.1104/pp.113.4.1009 pmid:9112764 pmcid:PMC158223 fatcat:znrzfbpdqjft7dwivsia62hy2i

Reengineering the Oligosaccharide Specificity of CVN with BP_Dock

Ashini Bolia, Brian Woodrum, Banu Ozkan, Giovanna Ghirlanda
2013 Biophysical Journal  
Enhancing Human Spermine Synthase Activity by Site Directed Mutations Zhe Zhang 1,2 , Anthony Pegg 3 , Yoshihiko Ikeguchi 4 , Emil Alexov 1 . 1 Clemson University, Clemson, SC, USA, 2 University of Paris  ...  Spermine Synthase (SMS) is an enzyme converting spermidine into spermine, both of which are polyamines controlling normal cell growth and development.  ... 
doi:10.1016/j.bpj.2012.11.2114 fatcat:xm2masde65bmviy3udstk3ccrm

Interferons: Reprogramming the Metabolic Network against Viral Infection

Kavita Raniga, Chen Liang
2018 Viruses  
Recent studies have started to illuminate on the specific role of interferon in rewiring cellular metabolism to activate immune cells and limit viral infection.  ...  Interferons are cytokines that enhances the transcription of hundreds of interferon-stimulated genes (ISGs) whose products are key players in the innate immune response to viral infection.  ...  Acknowledgments: This work was supported by funding from Canadian Institutes of Health Research to Chen Liang. Author Contributions: Kavita Raniga and Chen Liang prepared the manuscript.  ... 
doi:10.3390/v10010036 pmid:29342871 pmcid:PMC5795449 fatcat:x3o5f4w4kfgqjl6q5hbc732vyq

Oil for the cancer engine: The cross-talk between oncogenic signaling and polyamine metabolism

Amaia Arruabarrena-Aristorena, Amaia Zabala-Letona, Arkaitz Carracedo
2018 Science Advances  
In contrast to the view of metabolites as fuel (anabolic intermediates) for cancer cells, polyamines are better defined as the oil that lubricates the cancer engine because they affect the activity of  ...  In this review, we enumerate and discuss current views of the regulation and activity of polyamine metabolism in tumor cell biology.  ...  Spermidine can react with a second dcSAM molecule through the action of spermine synthase to produce spermine and an additional MTA molecule.  ... 
doi:10.1126/sciadv.aar2606 pmid:29376126 pmcid:PMC5783676 fatcat:wpubsrgihbhedezxnhqasxg4re

Targeting Polyamines and Inflammation for Cancer Prevention [chapter]

Naveen Babbar, Eugene W. Gerner
2010 Recent Results in Cancer Research  
These include reactions catalyzed by the biosynthetic enzymes, ornithine decarboxylase (ODC), Sadenosylmethionine decarboxylase (SAMDC), and the spermidine and spermine synthases.  ...  Targeting polyamine metabolism (by use of polyamine synthesis inhibitors or polyamine catabolism activators) and inflammation (by use of nonsteroidal anti-inflammatory drugs) has been studied for many  ...  As shown in this figure, the activity of the surface transporter to import aiginine can be enhanced by increasing polyamine synthesis and/or export, as occurs in human prostate carcinogenesis (Bettuzzi  ... 
doi:10.1007/978-3-642-10858-7_4 pmid:21253788 pmcid:PMC3587145 fatcat:r6c5oel5tzawtasydgeyvcisry

Citrus Polyamines: Structure, Biosynthesis, and Physiological Functions

Nabil Killiny, Yasser Nehela
2020 Plants  
We believe that the molecular and biochemical understanding of PAs metabolism and their physiological roles in citrus plants will help citrus breeding programs to enhance tolerance to biotic and abiotic  ...  genetic engineering.  ...  SAMS: S-Adenosyl-methionine synthase, SPDS: Spermidine synthase, SPMS: Spermine synthase, and TSS: Thermospermine synthase encoded by ACAULIS5 (ACL5).  ... 
doi:10.3390/plants9040426 pmid:32244406 fatcat:s7roriuakfdbvojdcqyygpgfn4

Novel Chimeric Spermidine Synthase-Saccharopine Dehydrogenase Gene (SPE3-LYS9) in the Human PathogenCryptococcus neoformans

Joanne M. Kingsbury, Zhonghui Yang, Tonya M. Ganous, Gary M. Cox, John H. McCusker
2004 Eukaryotic Cell  
In contrast toSaccharomyces cerevisiae spe3mutants, the polyamine auxotrophy ofC. neoformans spe3-LYS9mutants was not satisfied by spermine.  ...  Thus,SPE3-LYS9encodes functional spermidine synthase and saccharopine dehydrogenase gene products.  ...  This work was supported by a Public Health Service grant from NIAID (PO1-AI44975).  ... 
doi:10.1128/ec.3.3.752-763.2004 pmid:15189996 pmcid:PMC420128 fatcat:juqy5rf3wrgaxnlvafwaqog6du

Polyamines and transglutaminases: biological, clinical, and biotechnological perspectives

Enzo Agostinelli
2014 Amino Acids  
The mechanisms which lead to enhanced proliferation are unknown. Modification of eIF-5A involves two catalytic steps by deoxyhypusine synthase (DHS) and deoxhypusine hydroxylase (DOHH).  ...  BSAO and spermine association in multidrug resistant cells, sensitized to spermine metabolites by an increased mitochondrial activity, and mammals spermine oxidase are differentially activated in tissues  ... 
doi:10.1007/s00726-014-1688-0 pmid:24553826 fatcat:yudjhpfqevbnpkwgqsugt3dvqm

Combination Chemoprevention for Colon Cancer Targeting Polyamine Synthesis and Inflammation

E. W. Gerner, F. L. Meyskens
2009 Clinical Cancer Research  
Increased polyamine synthesis and inflammation have long been associated with colon carcinogenesis in both preclinical models and in humans.  ...  synthesis and inflammation can be an effective strategy for preventing the occurrence of the advanced and/or multiple adenomas that are most closely associated with the development of colon cancers in humans  ...  This bile acid -induced inflammatory response is suppressed by loss of nitric oxide synthase 2 alleles in genetically engineered mice (18) , which imply a role for the nitric oxide synthase 2 substrate  ... 
doi:10.1158/1078-0432.ccr-08-2235 pmid:19188144 pmcid:PMC2666541 fatcat:xmuvbiajirbd5dnfozoswqvwya
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