Identification of a Potential Inhibitor Targeting MurC Ligase of the Drug Resistant Pseudomonas aeruginosa Strain through Structure-Based Virtual Screening Approach and In Vitro Assay.
Identifieur interne : 000237 ( PubMed/Corpus ); précédent : 000236; suivant : 000238Identification of a Potential Inhibitor Targeting MurC Ligase of the Drug Resistant Pseudomonas aeruginosa Strain through Structure-Based Virtual Screening Approach and In Vitro Assay.
Auteurs : Abdelmonaem Messaoudi ; Manel Zoghlami ; Zarrin Basharat ; Najla Sadfi-ZouaouiSource :
- Current pharmaceutical biotechnology [ 1873-4316 ] ; 2019.
English descriptors
- KwdEn :
- Amino Acid Sequence (MeSH), Anti-Bacterial Agents (chemistry), Anti-Bacterial Agents (pharmacology), Drug Discovery (methods), Drug Resistance, Bacterial (drug effects), Drug Resistance, Bacterial (genetics), Escherichia coli (drug effects), High-Throughput Screening Assays (MeSH), Humans (MeSH), Molecular Dynamics Simulation (MeSH), Peptide Synthases (antagonists & inhibitors), Peptide Synthases (genetics), Peptidoglycan (metabolism), Pseudomonas aeruginosa (drug effects), Pseudomonas aeruginosa (enzymology), Structure-Activity Relationship (MeSH).
- MESH :
- chemical , antagonists & inhibitors : Peptide Synthases.
- chemical , chemistry : Anti-Bacterial Agents.
- chemical , genetics : Peptide Synthases.
- chemical , metabolism : Peptidoglycan.
- chemical , pharmacology : Anti-Bacterial Agents.
- drug effects : Drug Resistance, Bacterial, Escherichia coli, Pseudomonas aeruginosa.
- enzymology : Pseudomonas aeruginosa.
- genetics : Drug Resistance, Bacterial.
- methods : Drug Discovery.
- Amino Acid Sequence, High-Throughput Screening Assays, Humans, Molecular Dynamics Simulation, Structure-Activity Relationship.
Abstract
BACKGROUND & OBJECTIVE
Pseudomonas aeruginosa shows resistance to a large number of antibiotics, including carbapenems and third generation cephalosporin. According to the World Health Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a good target for the discovery of novel antimicrobial drugs.
METHODS
Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target for the design of new classes of antimicrobial inhibitors in gram-negative bacteria.
RESULTS
In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally through inhibition assay.
CONCLUSION
The presented results based on combined computational and in vitro analysis open up new horizons for the development of novel antimicrobials against this pathogen.
DOI: 10.2174/1389201020666190719123133
PubMed: 31333120
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pubmed:31333120Le document en format XML
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Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</nlm:affiliation></affiliation></author><author><name sortKey="Basharat, Zarrin" sort="Basharat, Zarrin" uniqKey="Basharat Z" first="Zarrin" last="Basharat">Zarrin Basharat</name><affiliation><nlm:affiliation>Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire Génomique, Bioinformatique et Chimie Moléculaire (GBCM, Conservatoire National des Arts et Métiers, Paris, 75003, France.</nlm:affiliation></affiliation></author><author><name sortKey="Sadfi Zouaoui, Najla" sort="Sadfi Zouaoui, Najla" uniqKey="Sadfi Zouaoui N" first="Najla" last="Sadfi-Zouaoui">Najla Sadfi-Zouaoui</name><affiliation><nlm:affiliation>Laboratoire de Mycologie, Pathologies et 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of Biotechnology of Béja, University of Jendouba, Avenue Habib Bourguiba, Béja 9000, Tunisia.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Mycologie, Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</nlm:affiliation></affiliation></author><author><name sortKey="Zoghlami, Manel" sort="Zoghlami, Manel" uniqKey="Zoghlami M" first="Manel" last="Zoghlami">Manel Zoghlami</name><affiliation><nlm:affiliation>Laboratoire de Mycologie, Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</nlm:affiliation></affiliation></author><author><name sortKey="Basharat, Zarrin" sort="Basharat, Zarrin" uniqKey="Basharat Z" first="Zarrin" last="Basharat">Zarrin Basharat</name><affiliation><nlm:affiliation>Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire Génomique, Bioinformatique et Chimie Moléculaire (GBCM, Conservatoire National des Arts et Métiers, Paris, 75003, France.</nlm:affiliation></affiliation></author><author><name sortKey="Sadfi Zouaoui, Najla" sort="Sadfi Zouaoui, Najla" uniqKey="Sadfi Zouaoui N" first="Najla" last="Sadfi-Zouaoui">Najla Sadfi-Zouaoui</name><affiliation><nlm:affiliation>Laboratoire de Mycologie, Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Current pharmaceutical biotechnology</title><idno type="eISSN">1873-4316</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence (MeSH)</term><term>Anti-Bacterial Agents (chemistry)</term><term>Anti-Bacterial Agents (pharmacology)</term><term>Drug Discovery (methods)</term><term>Drug Resistance, Bacterial (drug effects)</term><term>Drug Resistance, Bacterial (genetics)</term><term>Escherichia coli (drug effects)</term><term>High-Throughput Screening Assays (MeSH)</term><term>Humans (MeSH)</term><term>Molecular Dynamics Simulation (MeSH)</term><term>Peptide Synthases (antagonists & inhibitors)</term><term>Peptide Synthases (genetics)</term><term>Peptidoglycan (metabolism)</term><term>Pseudomonas aeruginosa (drug effects)</term><term>Pseudomonas aeruginosa (enzymology)</term><term>Structure-Activity Relationship (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Peptide Synthases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-Bacterial Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptide Synthases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptidoglycan</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Bacterial Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Drug Resistance, Bacterial</term><term>Escherichia coli</term><term>Pseudomonas aeruginosa</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Pseudomonas aeruginosa</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Drug Resistance, Bacterial</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Discovery</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Molecular Dynamics Simulation</term><term>Structure-Activity Relationship</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND & OBJECTIVE</b></p><p>Pseudomonas aeruginosa shows resistance to a large number of antibiotics, including carbapenems and third generation cephalosporin. According to the World Health Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a good target for the discovery of novel antimicrobial drugs.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target for the design of new classes of antimicrobial inhibitors in gram-negative bacteria.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally through inhibition assay.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>The presented results based on combined computational and in vitro analysis open up new horizons for the development of novel antimicrobials against this pathogen.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Curated" Owner="NLM"><PMID Version="1">31333120</PMID><DateCompleted><Year>2020</Year><Month>02</Month><Day>05</Day></DateCompleted><DateRevised><Year>2020</Year><Month>02</Month><Day>05</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1873-4316</ISSN><JournalIssue CitedMedium="Internet"><Volume>20</Volume><Issue>14</Issue><PubDate><Year>2019</Year></PubDate></JournalIssue><Title>Current pharmaceutical biotechnology</Title><ISOAbbreviation>Curr Pharm Biotechnol</ISOAbbreviation></Journal><ArticleTitle>Identification of a Potential Inhibitor Targeting MurC Ligase of the Drug Resistant Pseudomonas aeruginosa Strain through Structure-Based Virtual Screening Approach and In Vitro Assay.</ArticleTitle><Pagination><MedlinePgn>1203-1212</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.2174/1389201020666190719123133</ELocationID><Abstract><AbstractText Label="BACKGROUND & OBJECTIVE" NlmCategory="OBJECTIVE">Pseudomonas aeruginosa shows resistance to a large number of antibiotics, including carbapenems and third generation cephalosporin. According to the World Health Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a good target for the discovery of novel antimicrobial drugs.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target for the design of new classes of antimicrobial inhibitors in gram-negative bacteria.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally through inhibition assay.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">The presented results based on combined computational and in vitro analysis open up new horizons for the development of novel antimicrobials against this pathogen.</AbstractText><CopyrightInformation>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Messaoudi</LastName><ForeName>Abdelmonaem</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>The Higher Institute of Biotechnology of Béja, University of Jendouba, Avenue Habib Bourguiba, Béja 9000, Tunisia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Mycologie, Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zoghlami</LastName><ForeName>Manel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Laboratoire de Mycologie, Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Basharat</LastName><ForeName>Zarrin</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire Génomique, Bioinformatique et Chimie Moléculaire (GBCM, Conservatoire National des Arts et Métiers, Paris, 75003, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sadfi-Zouaoui</LastName><ForeName>Najla</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Laboratoire de Mycologie, Pathologies et Biomarqueurs, Faculté des Sciences de Tunis, Université de Tunis El Manar 2092, Tunis, Tunisia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Curr Pharm Biotechnol</MedlineTA><NlmUniqueID>100960530</NlmUniqueID><ISSNLinking>1389-2010</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010457">Peptidoglycan</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.2.-</RegistryNumber><NameOfSubstance UI="D010453">Peptide 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MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004926" MajorTopicYN="N">Escherichia coli</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D057166" MajorTopicYN="N">High-Throughput Screening Assays</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056004" MajorTopicYN="Y">Molecular Dynamics Simulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010453" MajorTopicYN="N">Peptide Synthases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010457" MajorTopicYN="N">Peptidoglycan</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011550" MajorTopicYN="N">Pseudomonas aeruginosa</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MurC ligase</Keyword><Keyword MajorTopicYN="N">P. aeruginosa</Keyword><Keyword MajorTopicYN="N">molecular docking</Keyword><Keyword MajorTopicYN="N">peptidoglycan</Keyword><Keyword MajorTopicYN="N">structure modeling</Keyword><Keyword MajorTopicYN="N">virtual screening.</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>03</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>06</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>07</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31333120</ArticleId><ArticleId IdType="pii">CPB-EPUB-99776</ArticleId><ArticleId IdType="doi">10.2174/1389201020666190719123133</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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