Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target
The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug‐resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This...
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| Veröffentlicht in: | Protein science 2013-06, Vol.22 (6), p.762-773 |
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| container_title | Protein science |
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| creator | Pendini, Nicole R. Yap, Min Y. Polyak, Steven W. Cowieson, Nathan P. Abell, Andrew Booker, Grant W. Wallace, John C. Wilce, Jacqueline A. Wilce, Matthew C. J. |
| description | The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug‐resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo‐ and apo‐forms of SaBPL using X‐ray crystallography. We also present small‐angle X‐ray scattering data of SaBPL in complex with its biotin‐carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl‐5′‐AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery.
PDB Code(s): 3RIR, 3RKY, 3RKX |
| doi_str_mv | 10.1002/pro.2262 |
| format | Article |
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PDB Code(s): 3RIR, 3RKY, 3RKX</description><identifier>ISSN: 0961-8368</identifier><identifier>EISSN: 1469-896X</identifier><identifier>DOI: 10.1002/pro.2262</identifier><identifier>PMID: 23559560</identifier><identifier>CODEN: PRCIEI</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acetyl-CoA Carboxylase - metabolism ; Adenosine Monophosphate - analogs & derivatives ; Adenosine Monophosphate - metabolism ; Amino Acid Sequence ; Antibiotics ; bacterial enzyme ; Biotin - analogs & derivatives ; Biotin - metabolism ; biotin protein ligase ; biotinylation ; biotin‐carboxyl carrier protein ; Carbon-Nitrogen Ligases - chemistry ; Carbon-Nitrogen Ligases - metabolism ; Crystallography, X-Ray ; DNA‐binding ; Enzymes ; Fatty Acid Synthase, Type II - metabolism ; Humans ; Molecular Sequence Data ; Protein Interaction Maps ; Protein Multimerization ; Proteins ; Sequence Alignment ; small‐angle X‐ray scattering ; Staphylococcal Infections - drug therapy ; Staphylococcal Infections - microbiology ; Staphylococcus aureus - chemistry ; Staphylococcus aureus - enzymology ; Staphylococcus aureus - metabolism</subject><ispartof>Protein science, 2013-06, Vol.22 (6), p.762-773</ispartof><rights>2013 The Protein Society</rights><rights>2013 The Protein Society.</rights><rights>2013 The Protein Society 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4052-510c6be6c7e72b599de9a5750e2e186b647a61c721a270d81da986d6f4c60fe53</citedby><cites>FETCH-LOGICAL-c4052-510c6be6c7e72b599de9a5750e2e186b647a61c721a270d81da986d6f4c60fe53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690716/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690716/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23559560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pendini, Nicole R.</creatorcontrib><creatorcontrib>Yap, Min Y.</creatorcontrib><creatorcontrib>Polyak, Steven W.</creatorcontrib><creatorcontrib>Cowieson, Nathan P.</creatorcontrib><creatorcontrib>Abell, Andrew</creatorcontrib><creatorcontrib>Booker, Grant W.</creatorcontrib><creatorcontrib>Wallace, John C.</creatorcontrib><creatorcontrib>Wilce, Jacqueline A.</creatorcontrib><creatorcontrib>Wilce, Matthew C. J.</creatorcontrib><title>Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target</title><title>Protein science</title><addtitle>Protein Sci</addtitle><description>The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug‐resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo‐ and apo‐forms of SaBPL using X‐ray crystallography. We also present small‐angle X‐ray scattering data of SaBPL in complex with its biotin‐carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl‐5′‐AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery.
PDB Code(s): 3RIR, 3RKY, 3RKX</description><subject>Acetyl-CoA Carboxylase - metabolism</subject><subject>Adenosine Monophosphate - analogs & derivatives</subject><subject>Adenosine Monophosphate - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Antibiotics</subject><subject>bacterial enzyme</subject><subject>Biotin - analogs & derivatives</subject><subject>Biotin - metabolism</subject><subject>biotin protein ligase</subject><subject>biotinylation</subject><subject>biotin‐carboxyl carrier protein</subject><subject>Carbon-Nitrogen Ligases - chemistry</subject><subject>Carbon-Nitrogen Ligases - metabolism</subject><subject>Crystallography, X-Ray</subject><subject>DNA‐binding</subject><subject>Enzymes</subject><subject>Fatty Acid Synthase, Type II - metabolism</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Protein Interaction Maps</subject><subject>Protein Multimerization</subject><subject>Proteins</subject><subject>Sequence Alignment</subject><subject>small‐angle X‐ray scattering</subject><subject>Staphylococcal Infections - drug therapy</subject><subject>Staphylococcal Infections - microbiology</subject><subject>Staphylococcus aureus - chemistry</subject><subject>Staphylococcus aureus - enzymology</subject><subject>Staphylococcus aureus - metabolism</subject><issn>0961-8368</issn><issn>1469-896X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV9rFTEQxYNY7LUKfgIJ-NKXbZPsJrvxQSjFf1CoWAXfwmx29t6UbbImWeX66c3tbYt98OkQ5jdnJnMIecXZCWdMnM4xnAihxBOy4o3SVafVj6dkxbTiVVer7pA8T-maMdZwUT8jh6KWUkvFVmR7leNi8xJhonYDEWzG6P5AdsHTMNKrDPNmOwUbrF0ShSVikd6F7DwtYzMWndwaElLwA3W-9BeTXfsMMXuM6S0986WY3W2bpRniGvMLcjDClPDlnR6R7x_efzv_VF1cfvx8fnZR2YZJUUnOrOpR2RZb0UutB9QgW8lQIO9Ur5oWFLet4CBaNnR8AN2pQY2NVWxEWR-Rd3vfeelvcLDoc_msmaO7gbg1AZx5XPFuY9bhl6mVZi1XxeDNnUEMPxdM2VyHJfqys-HljjUrF24KdbynbAwpRRwfJnBmdiGVdzC7kAr6-t-NHsD7VApQ7YHfbsLtf43Ml6-Xt4Z_AQQ-n1k</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>Pendini, Nicole R.</creator><creator>Yap, Min Y.</creator><creator>Polyak, Steven W.</creator><creator>Cowieson, Nathan P.</creator><creator>Abell, Andrew</creator><creator>Booker, Grant W.</creator><creator>Wallace, John C.</creator><creator>Wilce, Jacqueline A.</creator><creator>Wilce, Matthew C. J.</creator><general>Wiley Subscription Services, Inc</general><general>Blackwell Publishing Ltd</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>7QO</scope><scope>7T5</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>201306</creationdate><title>Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target</title><author>Pendini, Nicole R. ; Yap, Min Y. ; Polyak, Steven W. ; Cowieson, Nathan P. ; Abell, Andrew ; Booker, Grant W. ; Wallace, John C. ; Wilce, Jacqueline A. ; Wilce, Matthew C. J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4052-510c6be6c7e72b599de9a5750e2e186b647a61c721a270d81da986d6f4c60fe53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetyl-CoA Carboxylase - metabolism</topic><topic>Adenosine Monophosphate - analogs & derivatives</topic><topic>Adenosine Monophosphate - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Antibiotics</topic><topic>bacterial enzyme</topic><topic>Biotin - analogs & derivatives</topic><topic>Biotin - metabolism</topic><topic>biotin protein ligase</topic><topic>biotinylation</topic><topic>biotin‐carboxyl carrier protein</topic><topic>Carbon-Nitrogen Ligases - chemistry</topic><topic>Carbon-Nitrogen Ligases - metabolism</topic><topic>Crystallography, X-Ray</topic><topic>DNA‐binding</topic><topic>Enzymes</topic><topic>Fatty Acid Synthase, Type II - metabolism</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>Protein Interaction Maps</topic><topic>Protein Multimerization</topic><topic>Proteins</topic><topic>Sequence Alignment</topic><topic>small‐angle X‐ray scattering</topic><topic>Staphylococcal Infections - drug therapy</topic><topic>Staphylococcal Infections - microbiology</topic><topic>Staphylococcus aureus - chemistry</topic><topic>Staphylococcus aureus - enzymology</topic><topic>Staphylococcus aureus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pendini, Nicole R.</creatorcontrib><creatorcontrib>Yap, Min Y.</creatorcontrib><creatorcontrib>Polyak, Steven W.</creatorcontrib><creatorcontrib>Cowieson, Nathan P.</creatorcontrib><creatorcontrib>Abell, Andrew</creatorcontrib><creatorcontrib>Booker, Grant W.</creatorcontrib><creatorcontrib>Wallace, John C.</creatorcontrib><creatorcontrib>Wilce, Jacqueline A.</creatorcontrib><creatorcontrib>Wilce, Matthew C. J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Protein science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pendini, Nicole R.</au><au>Yap, Min Y.</au><au>Polyak, Steven W.</au><au>Cowieson, Nathan P.</au><au>Abell, Andrew</au><au>Booker, Grant W.</au><au>Wallace, John C.</au><au>Wilce, Jacqueline A.</au><au>Wilce, Matthew C. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target</atitle><jtitle>Protein science</jtitle><addtitle>Protein Sci</addtitle><date>2013-06</date><risdate>2013</risdate><volume>22</volume><issue>6</issue><spage>762</spage><epage>773</epage><pages>762-773</pages><issn>0961-8368</issn><eissn>1469-896X</eissn><coden>PRCIEI</coden><abstract>The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug‐resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo‐ and apo‐forms of SaBPL using X‐ray crystallography. We also present small‐angle X‐ray scattering data of SaBPL in complex with its biotin‐carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl‐5′‐AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery.
PDB Code(s): 3RIR, 3RKY, 3RKX</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23559560</pmid><doi>10.1002/pro.2262</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Protein science, 2013-06, Vol.22 (6), p.762-773 |
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| source | Wiley Free Content; Wiley Online Library - AutoHoldings Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acetyl-CoA Carboxylase - metabolism Adenosine Monophosphate - analogs & derivatives Adenosine Monophosphate - metabolism Amino Acid Sequence Antibiotics bacterial enzyme Biotin - analogs & derivatives Biotin - metabolism biotin protein ligase biotinylation biotin‐carboxyl carrier protein Carbon-Nitrogen Ligases - chemistry Carbon-Nitrogen Ligases - metabolism Crystallography, X-Ray DNA‐binding Enzymes Fatty Acid Synthase, Type II - metabolism Humans Molecular Sequence Data Protein Interaction Maps Protein Multimerization Proteins Sequence Alignment small‐angle X‐ray scattering Staphylococcal Infections - drug therapy Staphylococcal Infections - microbiology Staphylococcus aureus - chemistry Staphylococcus aureus - enzymology Staphylococcus aureus - metabolism |
| title | Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target |
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