Pseudomonas aeruginosa Dps (PA0962) Functions in H 2 O 2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity
We report the structural, biochemical, and functional characterization of the product of gene PA0962 from PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH...
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| Veröffentlicht in: | International journal of molecular sciences 2023-02, Vol.24 (5) |
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| container_title | International journal of molecular sciences |
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| creator | Rajapaksha, Nimesha Soldano, Anabel Yao, Huili Donnarumma, Fabrizio Kashipathy, Maithri M Seibold, Steve Battaile, Kevin P Lovell, Scott Rivera, Mario |
| description | We report the structural, biochemical, and functional characterization of the product of gene PA0962 from
PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe
utilizing H
O
(not O
) as an oxidant, suggesting Pa Dps functions to aid
to survive H
O
-mediated oxidative stress. In agreement, a
Δ
mutant is significantly more susceptible to H
O
than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe
oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H
O
or O
but requires divalent cations and 12-mer Pa Dps. |
| doi_str_mv | 10.3390/ijms24054669 |
| format | Article |
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PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe
utilizing H
O
(not O
) as an oxidant, suggesting Pa Dps functions to aid
to survive H
O
-mediated oxidative stress. In agreement, a
Δ
mutant is significantly more susceptible to H
O
than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe
oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H
O
or O
but requires divalent cations and 12-mer Pa Dps.</description><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24054669</identifier><identifier>PMID: 36902100</identifier><language>eng</language><publisher>Switzerland</publisher><subject>Bacterial Proteins - metabolism ; Cations, Divalent ; DNA - metabolism ; DNA Cleavage ; DNA-Binding Proteins - metabolism ; Hydrogen Peroxide - metabolism ; Iron - metabolism ; Oxidative Stress ; Pseudomonas aeruginosa - genetics ; Pseudomonas aeruginosa - metabolism</subject><ispartof>International journal of molecular sciences, 2023-02, Vol.24 (5)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-3215-4472 ; 0000-0002-5692-5497 ; 0000-0003-0833-3259</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36902100$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rajapaksha, Nimesha</creatorcontrib><creatorcontrib>Soldano, Anabel</creatorcontrib><creatorcontrib>Yao, Huili</creatorcontrib><creatorcontrib>Donnarumma, Fabrizio</creatorcontrib><creatorcontrib>Kashipathy, Maithri M</creatorcontrib><creatorcontrib>Seibold, Steve</creatorcontrib><creatorcontrib>Battaile, Kevin P</creatorcontrib><creatorcontrib>Lovell, Scott</creatorcontrib><creatorcontrib>Rivera, Mario</creatorcontrib><title>Pseudomonas aeruginosa Dps (PA0962) Functions in H 2 O 2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>We report the structural, biochemical, and functional characterization of the product of gene PA0962 from
PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe
utilizing H
O
(not O
) as an oxidant, suggesting Pa Dps functions to aid
to survive H
O
-mediated oxidative stress. In agreement, a
Δ
mutant is significantly more susceptible to H
O
than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe
oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H
O
or O
but requires divalent cations and 12-mer Pa Dps.</description><subject>Bacterial Proteins - metabolism</subject><subject>Cations, Divalent</subject><subject>DNA - metabolism</subject><subject>DNA Cleavage</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Iron - metabolism</subject><subject>Oxidative Stress</subject><subject>Pseudomonas aeruginosa - genetics</subject><subject>Pseudomonas aeruginosa - metabolism</subject><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFjjFPAkEQRjcmRhDtrM2UWqBzu8eaKy8cBAuBRGNLFnfAIdze5WbvAn-A3y2F1hZfXvPy8il1l-CTMRk-864UneIotTa7UP0k1XqIaF966lpkh6iNHmVXqmdshjpB7KvTUqj1VVkFJ-CoabccKnFQ1AIPyxwzqx9h2oavyFUQ4AAz0LA47408u0geFgf2LnJH8B4bEoGCNhSEwAUPk8M3rzkKvAb45NhUUMxzGO_JdRy2kJ-7HcfjjbrcuL3Q7S8H6n46-RjPhnW7Lsmv6oZL1xxXf8fNv8IPAs5RuA</recordid><startdate>20230228</startdate><enddate>20230228</enddate><creator>Rajapaksha, Nimesha</creator><creator>Soldano, Anabel</creator><creator>Yao, Huili</creator><creator>Donnarumma, Fabrizio</creator><creator>Kashipathy, Maithri M</creator><creator>Seibold, Steve</creator><creator>Battaile, Kevin P</creator><creator>Lovell, Scott</creator><creator>Rivera, Mario</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0002-3215-4472</orcidid><orcidid>https://orcid.org/0000-0002-5692-5497</orcidid><orcidid>https://orcid.org/0000-0003-0833-3259</orcidid></search><sort><creationdate>20230228</creationdate><title>Pseudomonas aeruginosa Dps (PA0962) Functions in H 2 O 2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity</title><author>Rajapaksha, Nimesha ; Soldano, Anabel ; Yao, Huili ; Donnarumma, Fabrizio ; Kashipathy, Maithri M ; Seibold, Steve ; Battaile, Kevin P ; Lovell, Scott ; Rivera, Mario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_369021003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Bacterial Proteins - metabolism</topic><topic>Cations, Divalent</topic><topic>DNA - metabolism</topic><topic>DNA Cleavage</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Iron - metabolism</topic><topic>Oxidative Stress</topic><topic>Pseudomonas aeruginosa - genetics</topic><topic>Pseudomonas aeruginosa - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rajapaksha, Nimesha</creatorcontrib><creatorcontrib>Soldano, Anabel</creatorcontrib><creatorcontrib>Yao, Huili</creatorcontrib><creatorcontrib>Donnarumma, Fabrizio</creatorcontrib><creatorcontrib>Kashipathy, Maithri M</creatorcontrib><creatorcontrib>Seibold, Steve</creatorcontrib><creatorcontrib>Battaile, Kevin P</creatorcontrib><creatorcontrib>Lovell, Scott</creatorcontrib><creatorcontrib>Rivera, Mario</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rajapaksha, Nimesha</au><au>Soldano, Anabel</au><au>Yao, Huili</au><au>Donnarumma, Fabrizio</au><au>Kashipathy, Maithri M</au><au>Seibold, Steve</au><au>Battaile, Kevin P</au><au>Lovell, Scott</au><au>Rivera, Mario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pseudomonas aeruginosa Dps (PA0962) Functions in H 2 O 2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-02-28</date><risdate>2023</risdate><volume>24</volume><issue>5</issue><eissn>1422-0067</eissn><abstract>We report the structural, biochemical, and functional characterization of the product of gene PA0962 from
PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe
utilizing H
O
(not O
) as an oxidant, suggesting Pa Dps functions to aid
to survive H
O
-mediated oxidative stress. In agreement, a
Δ
mutant is significantly more susceptible to H
O
than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe
oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H
O
or O
but requires divalent cations and 12-mer Pa Dps.</abstract><cop>Switzerland</cop><pmid>36902100</pmid><doi>10.3390/ijms24054669</doi><orcidid>https://orcid.org/0000-0002-3215-4472</orcidid><orcidid>https://orcid.org/0000-0002-5692-5497</orcidid><orcidid>https://orcid.org/0000-0003-0833-3259</orcidid></addata></record> |
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| ispartof | International journal of molecular sciences, 2023-02, Vol.24 (5) |
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| source | MEDLINE; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Bacterial Proteins - metabolism Cations, Divalent DNA - metabolism DNA Cleavage DNA-Binding Proteins - metabolism Hydrogen Peroxide - metabolism Iron - metabolism Oxidative Stress Pseudomonas aeruginosa - genetics Pseudomonas aeruginosa - metabolism |
| title | Pseudomonas aeruginosa Dps (PA0962) Functions in H 2 O 2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity |
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