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Title: Identification of aaNAT5b as a spermine N-acetyltransferase in the mosquito, Aedes aegypti

Abstract

Mosquitoes transmit a number of diseases in animals and humans, including Dengue, Chikungunya and Zika viruses that affect millions of people each year. Controlling the disease transmitting mosquitoes has proven to be a successful strategy to reduce the viruses transmission. Polyamines are required for the life cycle of the RNA viruses, Chikungunya virus and Zika virus, and a depletion of spermidine and spermine in the host via induction of spermine N-acetyltransferase restricts their replication. Spermine N-acetyltransferase is a key catabolic enzyme in the polyamine pathway, however there is no information of the enzyme identification in any insects. Aliphatic polyamines play a fundamental role in tissue growth and development in organisms. They are acetylated by spermidine/spermine N1-acetyltransferase (SAT). In this study we provided a molecular and biochemical identification of SAT from Aedes aegypti mosquitoes. Screening of purified recombinant proteins against polyamines established that aaNAT5b, named previously based on sequence similarity with identified aaNAT1 in insects, is active to spermine and spermidine. A crystal structure was determined and used in molecular docking in this study. Key residues were identified to be involved in spermine binding using molecular docking and simulation. In addition, SAT transcript was down regulated by blood feeding using amore » real time PCR test. Based on its substrate profile and transcriptional levels after blood feeding, together with previous reports for polyamines required in arboviruses replication, SAT might be potentially used as a target to control arboviruses with human interference.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [4];  [4];  [5];  [6]; ORCiD logo [1];
  1. Hainan Univ. (China). Key Lab. of Tropical Biological Resources of Ministry of Education; Hainan Univ. (China). Inst. of Tropical Agriculture and Forestry. Lab. of Tropical Veterinary Medical and Vector Biology
  2. Krantisinh Nana Patil College of Veterinary Science, Shirval (India)
  3. Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States). Dept. of Biochemistry
  4. Hainan Univ. (China). Inst. of Tropical Agriculture and Forestry. Lab. of Tropical Veterinary Medical and Vector Biology
  5. Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Dept.
  6. Krantisinh Nana Patil College of Veterinary Science, Shirval (India)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI Identifier:
1627856
Grant/Contract Number:  
SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 3; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics

Citation Formats

Guan, Huai, Wang, Maoying, Liao, Chenghong, Liang, Jing, Mehere, Prajwalini, Tian, Meiling, Liu, Hairong, Robinson, Howard, Li, Jianyong, Han, Qian, and Oliveira, Pedro L. Identification of aaNAT5b as a spermine N-acetyltransferase in the mosquito, Aedes aegypti. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0194499.
Guan, Huai, Wang, Maoying, Liao, Chenghong, Liang, Jing, Mehere, Prajwalini, Tian, Meiling, Liu, Hairong, Robinson, Howard, Li, Jianyong, Han, Qian, & Oliveira, Pedro L. Identification of aaNAT5b as a spermine N-acetyltransferase in the mosquito, Aedes aegypti. United States. https://doi.org/10.1371/journal.pone.0194499
Guan, Huai, Wang, Maoying, Liao, Chenghong, Liang, Jing, Mehere, Prajwalini, Tian, Meiling, Liu, Hairong, Robinson, Howard, Li, Jianyong, Han, Qian, and Oliveira, Pedro L. Mon . "Identification of aaNAT5b as a spermine N-acetyltransferase in the mosquito, Aedes aegypti". United States. https://doi.org/10.1371/journal.pone.0194499. https://www.osti.gov/servlets/purl/1627856.
@article{osti_1627856,
title = {Identification of aaNAT5b as a spermine N-acetyltransferase in the mosquito, Aedes aegypti},
author = {Guan, Huai and Wang, Maoying and Liao, Chenghong and Liang, Jing and Mehere, Prajwalini and Tian, Meiling and Liu, Hairong and Robinson, Howard and Li, Jianyong and Han, Qian and Oliveira, Pedro L.},
abstractNote = {Mosquitoes transmit a number of diseases in animals and humans, including Dengue, Chikungunya and Zika viruses that affect millions of people each year. Controlling the disease transmitting mosquitoes has proven to be a successful strategy to reduce the viruses transmission. Polyamines are required for the life cycle of the RNA viruses, Chikungunya virus and Zika virus, and a depletion of spermidine and spermine in the host via induction of spermine N-acetyltransferase restricts their replication. Spermine N-acetyltransferase is a key catabolic enzyme in the polyamine pathway, however there is no information of the enzyme identification in any insects. Aliphatic polyamines play a fundamental role in tissue growth and development in organisms. They are acetylated by spermidine/spermine N1-acetyltransferase (SAT). In this study we provided a molecular and biochemical identification of SAT from Aedes aegypti mosquitoes. Screening of purified recombinant proteins against polyamines established that aaNAT5b, named previously based on sequence similarity with identified aaNAT1 in insects, is active to spermine and spermidine. A crystal structure was determined and used in molecular docking in this study. Key residues were identified to be involved in spermine binding using molecular docking and simulation. In addition, SAT transcript was down regulated by blood feeding using a real time PCR test. Based on its substrate profile and transcriptional levels after blood feeding, together with previous reports for polyamines required in arboviruses replication, SAT might be potentially used as a target to control arboviruses with human interference.},
doi = {10.1371/journal.pone.0194499},
journal = {PLoS ONE},
number = 3,
volume = 13,
place = {United States},
year = {Mon Mar 19 00:00:00 EDT 2018},
month = {Mon Mar 19 00:00:00 EDT 2018}
}

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