The Crystal Structures of Four Peptide Deformylases Bound to the Antibiotic Actinonin Reveal Two Distinct Types: A Platform for the Structure-based Design of Antibacterial Agents
Bacterial peptide deformylase (PDF) belongs to a sub-family of metalloproteases that catalyse the removal of the N-terminal formyl group from newly synthesised proteins. PDF is essential in prokaryotes and conserved throughout the eubacteria. It is therefore considered an attractive target for devel...
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| Veröffentlicht in: | Journal of molecular biology 2002-07, Vol.320 (5), p.951-962 |
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| container_title | Journal of molecular biology |
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| creator | Guilloteau, Jean-Pierre Mathieu, Magali Giglione, Carmela Blanc, Véronique Dupuy, Alain Chevrier, Miline Gil, Patricia Famechon, Alain Meinnel, Thierry Mikol, Vincent |
| description | Bacterial peptide deformylase (PDF) belongs to a sub-family of metalloproteases that catalyse the removal of the N-terminal formyl group from newly synthesised proteins. PDF is essential in prokaryotes and conserved throughout the eubacteria. It is therefore considered an attractive target for developing new antibacterial agents. Here, we report the crystal structures of four bacterial deformylases, free or bound to the naturally occurring antibiotic actinonin, including two from the major bacterial pathogens
Pseudomonas aeruginosa and
Staphylococcus aureus. The overall tertiary structure is essentially conserved but shows significant differences, namely at the C terminus, which are directly related to the deformylase type (i.e. I or II) they belong to. The geometry around the catalytic metal ion exhibits a high level of similarity within the different enzymes, as does the binding mode of actinonin to the various deformylases. However, some significant structural differences are found in the vicinity of the active site, highlighting the structural and molecular requirements for the design of a deformylase inhibitor active against a broad spectrum of bacterial strains. |
| doi_str_mv | 10.1016/S0022-2836(02)00549-1 |
| format | Article |
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Pseudomonas aeruginosa and
Staphylococcus aureus. The overall tertiary structure is essentially conserved but shows significant differences, namely at the C terminus, which are directly related to the deformylase type (i.e. I or II) they belong to. The geometry around the catalytic metal ion exhibits a high level of similarity within the different enzymes, as does the binding mode of actinonin to the various deformylases. However, some significant structural differences are found in the vicinity of the active site, highlighting the structural and molecular requirements for the design of a deformylase inhibitor active against a broad spectrum of bacterial strains.</description><identifier>ISSN: 0022-2836</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1016/S0022-2836(02)00549-1</identifier><identifier>PMID: 12126617</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>actinonin ; Amidohydrolases ; Amino Acid Sequence ; Aminopeptidases ; Aminopeptidases - chemistry ; Anti-Bacterial Agents ; Anti-Bacterial Agents - chemistry ; antibiotic ; Bacillus stearothermophilus ; Binding Sites ; Catalytic Domain ; crystal structure ; Crystallography, X-Ray ; Escherichia coli ; Escherichia coli - enzymology ; Geobacillus stearothermophilus - enzymology ; Hydroxamic Acids ; Hydroxamic Acids - chemistry ; inhibitor ; Life Sciences ; metalloprotease ; Models, Molecular ; Molecular Sequence Data ; Nickel ; Nickel - chemistry ; Protein Structure, Tertiary ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - enzymology ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid ; Staphylococcus aureus ; Staphylococcus aureus - enzymology ; Vegetal Biology ; Zinc ; Zinc - chemistry</subject><ispartof>Journal of molecular biology, 2002-07, Vol.320 (5), p.951-962</ispartof><rights>2002 Elsevier Science Ltd</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-70eefcb27246cee80bc40e0cdab34b7d1108733cf6330478c6277c223b4f9a123</citedby><cites>FETCH-LOGICAL-c492t-70eefcb27246cee80bc40e0cdab34b7d1108733cf6330478c6277c223b4f9a123</cites><orcidid>0000-0001-5642-8637 ; 0000-0002-7475-1558</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022283602005491$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12126617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00140511$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Guilloteau, Jean-Pierre</creatorcontrib><creatorcontrib>Mathieu, Magali</creatorcontrib><creatorcontrib>Giglione, Carmela</creatorcontrib><creatorcontrib>Blanc, Véronique</creatorcontrib><creatorcontrib>Dupuy, Alain</creatorcontrib><creatorcontrib>Chevrier, Miline</creatorcontrib><creatorcontrib>Gil, Patricia</creatorcontrib><creatorcontrib>Famechon, Alain</creatorcontrib><creatorcontrib>Meinnel, Thierry</creatorcontrib><creatorcontrib>Mikol, Vincent</creatorcontrib><title>The Crystal Structures of Four Peptide Deformylases Bound to the Antibiotic Actinonin Reveal Two Distinct Types: A Platform for the Structure-based Design of Antibacterial Agents</title><title>Journal of molecular biology</title><addtitle>J Mol Biol</addtitle><description>Bacterial peptide deformylase (PDF) belongs to a sub-family of metalloproteases that catalyse the removal of the N-terminal formyl group from newly synthesised proteins. PDF is essential in prokaryotes and conserved throughout the eubacteria. It is therefore considered an attractive target for developing new antibacterial agents. Here, we report the crystal structures of four bacterial deformylases, free or bound to the naturally occurring antibiotic actinonin, including two from the major bacterial pathogens
Pseudomonas aeruginosa and
Staphylococcus aureus. The overall tertiary structure is essentially conserved but shows significant differences, namely at the C terminus, which are directly related to the deformylase type (i.e. I or II) they belong to. The geometry around the catalytic metal ion exhibits a high level of similarity within the different enzymes, as does the binding mode of actinonin to the various deformylases. However, some significant structural differences are found in the vicinity of the active site, highlighting the structural and molecular requirements for the design of a deformylase inhibitor active against a broad spectrum of bacterial strains.</description><subject>actinonin</subject><subject>Amidohydrolases</subject><subject>Amino Acid Sequence</subject><subject>Aminopeptidases</subject><subject>Aminopeptidases - chemistry</subject><subject>Anti-Bacterial Agents</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>antibiotic</subject><subject>Bacillus stearothermophilus</subject><subject>Binding Sites</subject><subject>Catalytic Domain</subject><subject>crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Escherichia coli</subject><subject>Escherichia coli - enzymology</subject><subject>Geobacillus stearothermophilus - enzymology</subject><subject>Hydroxamic Acids</subject><subject>Hydroxamic Acids - chemistry</subject><subject>inhibitor</subject><subject>Life Sciences</subject><subject>metalloprotease</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Nickel</subject><subject>Nickel - chemistry</subject><subject>Protein Structure, Tertiary</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa - enzymology</subject><subject>Sequence Analysis, Protein</subject><subject>Sequence Homology, Amino Acid</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - enzymology</subject><subject>Vegetal Biology</subject><subject>Zinc</subject><subject>Zinc - chemistry</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1vEzEQhi0EoqHwE0A-IXpYGH9kP7igJaUUKRIVDWfL651tjTbrYHuD8rf6C-tNonDsxZZmnnnf0cwQ8pbBRwYs_3QLwHnGS5F_AH4BMJdVxp6RGYOyyspclM_J7ISckVch_IFECVm-JGeMM57nrJiRh9U90oXfhah7ehv9aOLoMVDX0Ss3enqDm2hbpJfYOb_e9Tqk5Fc3Di2NjsZUXA_RNtZFa2htoh3cYAf6C7eYBFf_HL20IUVNpKvdBsNnWtObXsdJjaZnL3HyzZqk3yazYO-GqYe9uDYRvU1y9R0OMbwmLzrdB3xz_M_J76tvq8V1tvz5_ceiXmZGVjxmBSB2puEFl7lBLKExEhBMqxshm6JlaVKFEKbLhQBZlCbnRWE4F43sKs24OCcXB9173auNt2vtd8ppq67rpZpiAEzCnLEtS-z7A7vx7u-IIaq1DQb7Xg_oxqAKVgkpxdMgKyWXpYAEzg-g8S4Ej92pBQZqugC1vwA1rVcBV_sLUJPBu6PB2Kyx_V91XHkCvhwATLPbWvQqGIuDwdZ6NFG1zj5h8QiobcGA</recordid><startdate>20020726</startdate><enddate>20020726</enddate><creator>Guilloteau, Jean-Pierre</creator><creator>Mathieu, Magali</creator><creator>Giglione, Carmela</creator><creator>Blanc, Véronique</creator><creator>Dupuy, Alain</creator><creator>Chevrier, Miline</creator><creator>Gil, Patricia</creator><creator>Famechon, Alain</creator><creator>Meinnel, Thierry</creator><creator>Mikol, Vincent</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-5642-8637</orcidid><orcidid>https://orcid.org/0000-0002-7475-1558</orcidid></search><sort><creationdate>20020726</creationdate><title>The Crystal Structures of Four Peptide Deformylases Bound to the Antibiotic Actinonin Reveal Two Distinct Types: A Platform for the Structure-based Design of Antibacterial Agents</title><author>Guilloteau, Jean-Pierre ; Mathieu, Magali ; Giglione, Carmela ; Blanc, Véronique ; Dupuy, Alain ; Chevrier, Miline ; Gil, Patricia ; Famechon, Alain ; Meinnel, Thierry ; Mikol, Vincent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-70eefcb27246cee80bc40e0cdab34b7d1108733cf6330478c6277c223b4f9a123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>actinonin</topic><topic>Amidohydrolases</topic><topic>Amino Acid Sequence</topic><topic>Aminopeptidases</topic><topic>Aminopeptidases - chemistry</topic><topic>Anti-Bacterial Agents</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>antibiotic</topic><topic>Bacillus stearothermophilus</topic><topic>Binding Sites</topic><topic>Catalytic Domain</topic><topic>crystal structure</topic><topic>Crystallography, X-Ray</topic><topic>Escherichia coli</topic><topic>Escherichia coli - enzymology</topic><topic>Geobacillus stearothermophilus - enzymology</topic><topic>Hydroxamic Acids</topic><topic>Hydroxamic Acids - chemistry</topic><topic>inhibitor</topic><topic>Life Sciences</topic><topic>metalloprotease</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Nickel</topic><topic>Nickel - chemistry</topic><topic>Protein Structure, Tertiary</topic><topic>Pseudomonas aeruginosa</topic><topic>Pseudomonas aeruginosa - enzymology</topic><topic>Sequence Analysis, Protein</topic><topic>Sequence Homology, Amino Acid</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - enzymology</topic><topic>Vegetal Biology</topic><topic>Zinc</topic><topic>Zinc - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guilloteau, Jean-Pierre</creatorcontrib><creatorcontrib>Mathieu, Magali</creatorcontrib><creatorcontrib>Giglione, Carmela</creatorcontrib><creatorcontrib>Blanc, Véronique</creatorcontrib><creatorcontrib>Dupuy, Alain</creatorcontrib><creatorcontrib>Chevrier, Miline</creatorcontrib><creatorcontrib>Gil, Patricia</creatorcontrib><creatorcontrib>Famechon, Alain</creatorcontrib><creatorcontrib>Meinnel, Thierry</creatorcontrib><creatorcontrib>Mikol, Vincent</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guilloteau, Jean-Pierre</au><au>Mathieu, Magali</au><au>Giglione, Carmela</au><au>Blanc, Véronique</au><au>Dupuy, Alain</au><au>Chevrier, Miline</au><au>Gil, Patricia</au><au>Famechon, Alain</au><au>Meinnel, Thierry</au><au>Mikol, Vincent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Crystal Structures of Four Peptide Deformylases Bound to the Antibiotic Actinonin Reveal Two Distinct Types: A Platform for the Structure-based Design of Antibacterial Agents</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2002-07-26</date><risdate>2002</risdate><volume>320</volume><issue>5</issue><spage>951</spage><epage>962</epage><pages>951-962</pages><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>Bacterial peptide deformylase (PDF) belongs to a sub-family of metalloproteases that catalyse the removal of the N-terminal formyl group from newly synthesised proteins. PDF is essential in prokaryotes and conserved throughout the eubacteria. It is therefore considered an attractive target for developing new antibacterial agents. Here, we report the crystal structures of four bacterial deformylases, free or bound to the naturally occurring antibiotic actinonin, including two from the major bacterial pathogens
Pseudomonas aeruginosa and
Staphylococcus aureus. The overall tertiary structure is essentially conserved but shows significant differences, namely at the C terminus, which are directly related to the deformylase type (i.e. I or II) they belong to. The geometry around the catalytic metal ion exhibits a high level of similarity within the different enzymes, as does the binding mode of actinonin to the various deformylases. However, some significant structural differences are found in the vicinity of the active site, highlighting the structural and molecular requirements for the design of a deformylase inhibitor active against a broad spectrum of bacterial strains.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>12126617</pmid><doi>10.1016/S0022-2836(02)00549-1</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-5642-8637</orcidid><orcidid>https://orcid.org/0000-0002-7475-1558</orcidid></addata></record> |
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| subjects | actinonin Amidohydrolases Amino Acid Sequence Aminopeptidases Aminopeptidases - chemistry Anti-Bacterial Agents Anti-Bacterial Agents - chemistry antibiotic Bacillus stearothermophilus Binding Sites Catalytic Domain crystal structure Crystallography, X-Ray Escherichia coli Escherichia coli - enzymology Geobacillus stearothermophilus - enzymology Hydroxamic Acids Hydroxamic Acids - chemistry inhibitor Life Sciences metalloprotease Models, Molecular Molecular Sequence Data Nickel Nickel - chemistry Protein Structure, Tertiary Pseudomonas aeruginosa Pseudomonas aeruginosa - enzymology Sequence Analysis, Protein Sequence Homology, Amino Acid Staphylococcus aureus Staphylococcus aureus - enzymology Vegetal Biology Zinc Zinc - chemistry |
| title | The Crystal Structures of Four Peptide Deformylases Bound to the Antibiotic Actinonin Reveal Two Distinct Types: A Platform for the Structure-based Design of Antibacterial Agents |
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