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Title: Behind Every Good Metabolite there is a Great Enzyme (and perhaps a structure)

Abstract

Today, due to great technological advancements, it is possible to study everything at the same time. This ability has given birth to “totality” studies in the fields of genomics, transcriptomics, proteomics, and metabolomics. In turn, the combined study of all these global analyses gave birth to the field of systems biology. Another “totality” field brought to life with new emerging technologies is structural genomics, an effort to determine the three-dimensional structure of every protein encoded in a genome. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a specialized structural genomics effort composed of academic (University of Washington), government (Pacific Northwest National Laboratory), not-for-profit (Seattle BioMed), and commercial (Emerald BioStructures) institutions that is funded by the National Institute of Allergy and Infectious Diseases (Federal Contract: HHSN272200700057C and HHSN27220120025C) to apply genome-scale approaches in solving protein structures from biodefense organisms, as well as those causing emerging and re-emerging disease. In five years over 540 structures have been deposited into the Protein Data Bank (PDB) by SSGICD. About one third of all SSGCID structures contain bound ligands, many of which are metabolites or metabolite analogues present in the cell. These proteins structures are the blueprints for the structure-based design of themore » next generation of drugs against bacterial pathogens and other infectious diseases. Many of the selected SSGCID targets are annotated enzymes from known metabolomic pathways essential to cellular vitality since selectively “knocking-out” one of the enzymes in an important pathway with a drug may be fatal to the organism. One reason metabolomic pathways are important is because of the small molecules, or metabolites, produced at various steps in these pathways and identified by metabolomic studies. Unlike genomics, transcriptomics, and proteomics that may be influenced by epigenetic, post-transcriptional, and post-translational modifications, respectively, the metabolites present in the cell at any one time represent downstream biochemical endproducts, and therefore, metabolite profiles may be most closely associated with a phenotype and provide valuable information for infectious disease research. Metabolomic data would be even more useful if it could be linked to the vast amount of structural genomics data. Towards this goal SSGCID has created an automated website (http://apps.sbri.org/SSGCIDTargetStatus/Pathway) that assigns selected SSGCID target proteins to MetaCyc pathways (http://metacyc.org/). Details of this website will be provided here. The SSGCID-Pathway website represents a first big step towards linking metabolites and metabolic pathways to structural genomic data with the goal of accelerating the discovery of new agents to battle infectious diseases.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1056148
Report Number(s):
PNNL-SA-91649
41092; 45802; 34699; 29292; 600306000
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Metabolomics, 2(6):Article No. e124
Additional Journal Information:
Journal Name: Metabolomics, 2(6):Article No. e124
Country of Publication:
United States
Language:
English
Subject:
structural biology; infectious diseases; metabolomics; systems biology; SSGCID; Environmental Molecular Sciences Laboratory

Citation Formats

Buchko, Garry W., Phan, Isabelle, Cron, Lisabeth, Stacy, Robin, Stewart, Lance J., Staker, Bart L., Edwards, Tom E., Varani, Gabriele, Van Voorhis, Wesley C., and Myler, Peter J. Behind Every Good Metabolite there is a Great Enzyme (and perhaps a structure). United States: N. p., 2012. Web.
Buchko, Garry W., Phan, Isabelle, Cron, Lisabeth, Stacy, Robin, Stewart, Lance J., Staker, Bart L., Edwards, Tom E., Varani, Gabriele, Van Voorhis, Wesley C., & Myler, Peter J. Behind Every Good Metabolite there is a Great Enzyme (and perhaps a structure). United States.
Buchko, Garry W., Phan, Isabelle, Cron, Lisabeth, Stacy, Robin, Stewart, Lance J., Staker, Bart L., Edwards, Tom E., Varani, Gabriele, Van Voorhis, Wesley C., and Myler, Peter J. Thu . "Behind Every Good Metabolite there is a Great Enzyme (and perhaps a structure)". United States.
@article{osti_1056148,
title = {Behind Every Good Metabolite there is a Great Enzyme (and perhaps a structure)},
author = {Buchko, Garry W. and Phan, Isabelle and Cron, Lisabeth and Stacy, Robin and Stewart, Lance J. and Staker, Bart L. and Edwards, Tom E. and Varani, Gabriele and Van Voorhis, Wesley C. and Myler, Peter J.},
abstractNote = {Today, due to great technological advancements, it is possible to study everything at the same time. This ability has given birth to “totality” studies in the fields of genomics, transcriptomics, proteomics, and metabolomics. In turn, the combined study of all these global analyses gave birth to the field of systems biology. Another “totality” field brought to life with new emerging technologies is structural genomics, an effort to determine the three-dimensional structure of every protein encoded in a genome. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a specialized structural genomics effort composed of academic (University of Washington), government (Pacific Northwest National Laboratory), not-for-profit (Seattle BioMed), and commercial (Emerald BioStructures) institutions that is funded by the National Institute of Allergy and Infectious Diseases (Federal Contract: HHSN272200700057C and HHSN27220120025C) to apply genome-scale approaches in solving protein structures from biodefense organisms, as well as those causing emerging and re-emerging disease. In five years over 540 structures have been deposited into the Protein Data Bank (PDB) by SSGICD. About one third of all SSGCID structures contain bound ligands, many of which are metabolites or metabolite analogues present in the cell. These proteins structures are the blueprints for the structure-based design of the next generation of drugs against bacterial pathogens and other infectious diseases. Many of the selected SSGCID targets are annotated enzymes from known metabolomic pathways essential to cellular vitality since selectively “knocking-out” one of the enzymes in an important pathway with a drug may be fatal to the organism. One reason metabolomic pathways are important is because of the small molecules, or metabolites, produced at various steps in these pathways and identified by metabolomic studies. Unlike genomics, transcriptomics, and proteomics that may be influenced by epigenetic, post-transcriptional, and post-translational modifications, respectively, the metabolites present in the cell at any one time represent downstream biochemical endproducts, and therefore, metabolite profiles may be most closely associated with a phenotype and provide valuable information for infectious disease research. Metabolomic data would be even more useful if it could be linked to the vast amount of structural genomics data. Towards this goal SSGCID has created an automated website (http://apps.sbri.org/SSGCIDTargetStatus/Pathway) that assigns selected SSGCID target proteins to MetaCyc pathways (http://metacyc.org/). Details of this website will be provided here. The SSGCID-Pathway website represents a first big step towards linking metabolites and metabolic pathways to structural genomic data with the goal of accelerating the discovery of new agents to battle infectious diseases.},
doi = {},
journal = {Metabolomics, 2(6):Article No. e124},
number = ,
volume = ,
place = {United States},
year = {2012},
month = {11}
}